CN103772399B - Preparation method and use of basic amino acid modified amidotetraphenylporphyrin compound - Google Patents
Preparation method and use of basic amino acid modified amidotetraphenylporphyrin compound Download PDFInfo
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Abstract
The invention discloses a basic amino acid modified amidotetraphenylporphyrin compound, and a preparation method and a use thereof. The basic amino acid modified amidotetraphenylporphyrin compound has the structure as shown in specification. The preparation method of the novel basic amino acid modified amidotetraphenylporphyrin compound is simple and easy to implement, and the novel basic amino acid modified amidotetraphenylporphyrin compound has relatively strong optical absorptivity and relatively high singlet oxygen yield, and also is good in biocompatibility and low in toxicity, and further has remarkable effects in the aspects of photodynamic antibiosis and photodynamic anti-tumor. The novel basic amino acid modified amidotetraphenylporphyrin compound has cationic charges under physiological conditions, is relatively wide in antibacterial spectrum and has excellent in tumor cell targeting property.
Description
Technical field
The invention belongs to organic synthesiss and drug world are and in particular to ammonia modified by the basic amino acid for optical dynamic therapy
The preparation method of base tetraphenylporphyrin compound and purposes, the more particularly to basic amino acid by protecting tertbutyloxycarbonyl
The mixed anhydride being formed with ethyl chloroformate and amino tetraphenylporphyrin are reacted and obtain basic amino acid modification amino tetraphenylporphyrin
Compound, and this basic amino acid modify amino tetraphenylporphyrin compound preparing light power antibacterial and light power antineoplastic agent
Application in thing.
Background technology
Photodynamic therapy (photodynamic therapy, pdt) is one and carries out disease using photodynamic reaction and examine
New technique that is disconnected and treating[1].The method that it passes through visible ray, near infrared light or ultraviolet light, drives in biological tissue and is in
The photosensitizer of excited state is interacted with oxygen molecule, produces singlet oxygen, superoxide radical, hydroxyl radical free radical or hydrogen peroxide etc.
High reaction activity material, acts on target cell and causes local photic damage, inducing cell death or microorganism deactivated, thus play controlling
Treatment effect [2].The advantage of photodynamic therapy is that toxicity is low, rapid-action, targeting strong, and does not endanger while killing proliferative cell
And normal structure[3].
Photosensitizer is a key factor affecting pdt curative effect in the selectivity positioning of target site and accumulation, clinical at present
It is currently in use or is in the photosensitizer of conceptual phase, including porphyrin, fluorine boron two pyroles, fullerene, phthalocyanines, phenothiazine
Class and methylene blue etc.[4].Wherein, porphyrinses are due to having good spectral characteristic and biocompatibility, high single line
State oxygen yield and being widely present in vivo, receives extensive research[5].Tetraphenylporphyrin is that a class druggability is good
Benzoporphyrin analog derivative, carries out modifying for chemical structure with tetraphenylporphyrin for parent, has the advantages that it is unique: 1. porphyrin ring tool
There are rigid structure, the direction of periphery functional group and position can preferably be controlled, be allowed to have and trim molecule between optimal
Interaction；2. the molecular area of compound is generally higher than 100, there is extensive spectral response range；3. Porphyrin Molecule exists
(600-700nm) has stronger absorption near infrared region, it is possible to use this wave band, as excitation wavelength, carries out pdt treatment[6].
Basic amino acid hydrolyze generation hydroxyl radical negative ion be more than hydrogen cation aminoacid (polarity is positively charged
Aminoacid), it is characterized in that side chain often contains the alkali electroless group that can protonate, such as guanidine radicals, amino, imidazole radicals[7].Alkaline ammonia
Base acid pharmaceutically has important value, and lysine can promote brain development and lipid metabolism, adjusts pineal gland, mammary gland, Huang
Body and ovary, prevent and treat cell degradation；The compound formulation that arginine and deoxycholic acid are made cures mainly syphilis, viral jaundice etc.
Active drug；Histidine can be also used for treating heart disease, anemia, rheumatic arthritis etc. as biochemical preparation[8-10].Will
When basic amino acid is used for the chemical modification of drug molecule, the amino on aminoacid and carboxyl can form hydrogen bond, Coulomb force, idol
Pole-dipole active force, the substituent group on alpha-carbon can be modified intermolecular generation electrostatic force, Van der Waals force, hydrophobic interaction, solid
Effect etc.[11-12].Therefore, the molecular characterization of aminoacid is made it suitable as modification group and is combined with drug molecule, reaches increasing
Strong drug solubility, the purpose reducing toxicity and improving targeting.
Three kinds of basic amino acids in present invention selection natural amino acid, l- lysine ((s) -2,6- diaminocaproic acid),
L- histidine ((s) -2- amino -3- (4- imidazole radicals) propanoic acid) and l- arginine ((s) -2- amino -5- guanidinopentanoic acid) conduct are repaiied
Decorations group, carries out conjugated with amino tetraphenylporphyrin, obtains the cation photosensitizer of series of new.Amino repaiied by basic amino acid
Tetraphenylporphyrin compound has that good water solubility, toxicity is low and the strong feature of targeting:
1. improve targeting.The positive charge group that such photosensitizer carries in physiological conditions is easily and on bacteria cell wall
Negative electricity group combine, improve the targeting to gram negative bacteria for the photosensitizer.Simultaneously because cation photosensitizer positioning
In mitochondrion, and the mitochondrial transmembrane potential of tumor cell is higher, and (- 180mv, transmembrane potential often increases 60mv, can make inside film
The concentration of this molecule increases by 10 times), therefore cation photosensitizer is easily gathered in tumor cell mitochondrion (optical dynamic therapy
Sensitive cellss device)[1,13-14].
2. increase water solublity.Tetraphenylporphyrin molecule, due to the structural symmetry of itself, has stronger hydrophobicity, even
After upper highly polar amino acid chain, hydrophilic significantly increases, and water solublity is also improved, and therefore basic amino acid is repaiied
Decorations amino tetraphenylporphyrin photosensitizer has preferable bioavailability[15].
3. reduce cytotoxicity.Lysine is essential amino acid, and arginine and histidine are the required ammonia of human body half
Base acid, therefore introduces basic amino acid after Porphyrin Molecule, can improve the biocompatibility of photosensitizer, reduces immunogenicity, keeps away
Exempt from the generation of untoward reaction[16].
Therefore, basic amino acid amino acid modified amino tetraphenylporphyrin compound is as novel cation photosensitizer not only
High-efficiency low-toxicity, and there is the strong advantage of good water solubility, targeting, optical dynamic therapy can be used for as third generation photosensitizer and lead
Domain, especially has important using value in light power antibacterial and light power anti-tumor aspect.
List of references
[1] Gu Ying. photodynamic therapy [m]. Beijing: People's Health Publisher, 2012:1-10.
[2] juzeniene a, nielsen k p, moan j.biophysical aspects of photodynamic
Therapy [j] .j environ pathol toxicol oncol, 2006,25 (1): 7-28.
[3] Xie Songmei, Fu Shiping. the therapeuticss feature of optical dynamic therapy medicine photosensitizer and clinical evaluation key element [j]. in
State's new drug magazine, 2008,17 (7): 618-624.
[4]wainwright m.photodynamic antimicrobial chemotherapy(pact)[j].j
Antimicrob chemother, 1998,42 (1): 13-28.
[5] stojiljkovic i, evavold b d, kumar v.antimicrobial properties of
Porphyrins [j] .expert opin investig drugs, 2001,10 (2): 309-320.
[6] how to always cherish the memory of. the synthesis of derivatives of porphyrin and antitumor activity [d]. Tianjin: University Of Tianjin, 2006:26-
27.
[7] Cui Ying. the impact [d] to hela cell proliferation and its telomerase activation for the basic amino acid. Shenyang: China Medical
University, 2005:1-10
[8] sol v, branland p, chaleix v, et al.amino porphyrins as
photoinhibitors of gramn-positive and-negative bacteria[j].bioorg med chem
Lett, 2004,14 (16): 4207-4211.
[9]tomJ p, neves m g, tomA c, et al.synthesis and antibacterial
Activity of new poly-s-lysine-porphyrin conjugates [j] .j med chem, 2004,47 (26):
6649-6652.
[10]bourrL, giuntini f, eggleston i m, et al.effective
photoinactivation of gram-positive and gram-negative bacterial strains using
An hiv-1tat peptide-porphyrin conjugate [j] .photochem photobiol sci, 2010,9
(12): 1613-1620.
[11] dosselli r, gobbo m, bolognini e, et al.porphyrin-apidaecin
Conjugate as a new broad spectrum antibacterial agent [j] .acs med chem lett,
2010,1 (1): 35-38.
[12] weimin s, gen z, guifu d, et aj.synthesis and in vitro pdt activity
Of miscellaneous porphyrins with amino acid and uracil [j] .bioorg med chem,
2008,16 (10): 5665-5671.
[13] alves e, costa l, carvalho c m, et al.charge effect on the
photoinactivation of gram-negative and gram-positive bacteria by cationic
Meso-substituted porphyrins [j] .bmc microbiol, 2009,9 (1): 70.
[14] Yu Kegui, Li Donghong, Zhou Chenghe, etc. the design synthesis of novel cation porphyrin and antimicrobial acivity
[j]. Third Military Medical University's journal, 2010,32 (1): 4145.
[15] Ye Yintao, Wang Chen. progress [a] the .2011 China pharmacy of amino acid derivatives antitumor action
Conference and the 11st Chinese pharmacists week collection of thesis [c]. Yantai: Chinese Pharmaceutical Association, 2011:1-6.
[16] Ji Guangjun. the synthesis [d] of amino acid modified double pyrazole quinoline derivant. Shihezi: Shihezi Univ, 2013:
7-11.
Content of the invention
It is an object of the invention to overcoming the deficiencies in the prior art, provide that a kind of good biocompatibility, toxicity be low, antibacterial is lived
Property high basic amino acid modify amino tetraphenylporphyrin compound.
Second object of the present invention is the preparation providing a kind of basic amino acid to modify amino tetraphenylporphyrin compound
Method.
Third object of the present invention is to provide a kind of basic amino acid to modify amino tetraphenylporphyrin compound as light
The purposes of power antibacterials.
Fourth object of the present invention is to provide a kind of basic amino acid to modify amino tetraphenylporphyrin compound as light
The purposes of power antitumor drug.
Technical scheme is summarized as follows:
A kind of basic amino acid is modified amino tetraphenylporphyrin compound and is had a structure in which
Wherein r1=h or-nh-x, r2=h or-nh-x, r3=h or-nh-x, r4=h or-nh-x, but r1、r2、r3、r4No
Can be h simultaneously；
The preparation method of amino tetraphenylporphyrin compound modified by a kind of basic amino acid, it is characterized in that tertbutyloxycarbonyl
(boc) basic amino acid protected and ethyl chloroformate react generation mixed anhydride, then react generation boc guarantor with amino tetraphenylporphyrin
The Amino acid porphyrins conjugatess of shield, finally hydrolyze de- boc protection and obtain basic amino acid modification amino tetraphenylporphyrin compound.
Described basic amino acid is modified amino tetraphenylporphyrin compound and is had a structure in which
Wherein r1=h or-nh-x, r2=h or-nh-x, r3=h or-nh-x, r4=h or-nh-x, but r1、r2、r3、r4No
Can be h simultaneously；
Said method is preferably: in proportion the basic amino acid of 0.09-1.5g boc protection is placed in reaction bulb, n2
The lower oxolane (thf) adding 7-20ml to be dried of protection, magneton stirs.It is cooled to -17 DEG C, add the triethylamine of 40-300 μ l
With the ethyl chloroformate of 27-300 μ l, react 1-3h, generate white precipitate, filter, discard precipitation.Take the amino of 0.01-1.5g
Tetraphenylporphyrin is dissolved in 5-30ml thf, and above-mentioned filtrate is added, and reaction 12-24h, thin layer chromatography (tlc) are stirred at room temperature
Monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash three times, obtain crude product,
Afterwards column chromatography for separation (dichloromethane: methanol: ammonia=500:1:2.5-30:1:0.4 or petroleum ether: ethyl acetate=10:1-3:
1) the basic amino acid porphyrin conjugates of boc protection are obtained.
The ch that the basic amino acid porphyrin conjugates of 50-100mg boc protection are dried with 10ml2cl2Dissolving, slow
Plus 10ml trifluoroacetic acid (tfa) (tfa/ch2cl2, 1/1, v/v), room temperature reaction 30min.Rotation removes solvent, adds absolute ether, raw
Become greenish precipitate, filter, precipitation dichloromethane and absolute ether respectively wash 2-3 time.With distilled water, green precipitate is molten again
Solution, ammonia adjusts ph7-8, separates out purple precipitation, filters, washes 2-3 time, and column chromatography for separation obtains basic amino acid and modifies amino
Tetraphenylporphyrin compound.
Described substituted porphyrin compound is 5- (o-amino-phenyl -) -10,15,20- Triphenylporphyrins, and 5,10- bis- is (o-
Aminophenyl) -15,20- diphenyl porphyrin, 5,15- bis- (o-amino-phenyl -) -10,20- diphenyl porphyrins, 5,10,15- tri-
(o-amino-phenyl -) -20- phenyl porphyrin, 5,10,15,20- tetra- (o-amino-phenyl -) porphyrin, 5- (m- aminophenyl) -10,
15,20- Triphenylporphyrins, 5,10-2 (m- aminophenyl) -15,20- diphenyl porphyrins, 5,15- bis- (m- aminophenyls) -
10,20- diphenyl porphyrins, 5,10,15- tri- (m- aminophenyl) -20- phenyl porphyrin, 5,10,15,20- tetra- (m- aminobenzenes
Base) porphyrin, 5- (p- aminophenyl) -10,15,20- Triphenylporphyrins, 5,10- bis- (p- aminophenyl) -15,20- diphenyl
Porphyrin, 5,15- bis- (p- aminophenyl) -10,20- diphenyl porphyrins, 5,10,15- tri- (p- aminophenyl) -20- phenyl porphin
Quinoline, 5,10,15,20- tetra- (p- aminophenyl) porphyrin.
A kind of basic amino acid is modified amino tetraphenylporphyrin compound and is being prepared light power antibacterial and light power antitumor
Application in medicine.
Novel alkaline Amino acid porphyrins conjugatess good biocompatibility involved in the present invention, toxicity is low.This system has
There is behavior in stronger light absorpting ability and higher singlet oxygen, have significant effect in light power antibiosis.The present invention
Preparation method succinctly easy.
Novel alkaline involved in the present invention amino acid modified amino tetraphenylporphyrin compounds process for production thereof is succinctly easy,
There is stronger light absorpting ability and higher singlet oxygen yield, and good biocompatibility, toxicity be low, in light power antibacterial and
Light power anti-tumor aspect has significant effect.The novel alkaline amino acid modified amino tetraphenylporphyrin compound of the present invention,
Carry cationic charge in physiological conditions, antimicrobial spectrum is wider, and has good tumor cell targeting.
Brief description
Fig. 1 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 1 basic amino acid.
Fig. 2 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 1 basic amino acid.
Fig. 3 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 2 basic amino acid.
Fig. 4 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 2 basic amino acid.
Fig. 5 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 3 basic amino acid.
Fig. 6 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 3 basic amino acid.
Fig. 7 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 4 basic amino acid.
Fig. 8 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 4 basic amino acid.
Fig. 9 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 5 basic amino acid.
Figure 10 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 5 basic amino acid.
Figure 11 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 6 basic amino acid.
Figure 12 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 6 basic amino acid.
Figure 13 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 7 basic amino acid.
Figure 14 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 7 basic amino acid.
Figure 15 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 8 basic amino acid.
Figure 16 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 8 basic amino acid.
Figure 17 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 9 basic amino acid.
Figure 18 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 9 basic amino acid.
Figure 19 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 10 basic amino acid.
Figure 20 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 11 basic amino acid.
Figure 21 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 11 basic amino acid.
Figure 22 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 12 basic amino acid.
Figure 23 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 12 basic amino acid.
Figure 24 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 13 basic amino acid.
Figure 25 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 13 basic amino acid.
Figure 26 is the synthetic route that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 14 basic amino acid.
Figure 27 is the high resolution mass spectrum that amino tetraphenylporphyrin compound modified by the embodiment of the present invention 14 basic amino acid.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated.Following examples are used for the present invention is described, but
It is not limited in these methods.
The system of embodiment 15- { 4- [(s) -2,6- two nitrilo caproamide base] phenyl } -10,15,20- Triphenylporphyrin (1d)
Standby
(s) -2,6- bis- t-butoxycarbonyl amino caproic acid (boc-lys (boc)-oh) (277.14mg, 0.80mmol) is put
In reaction bulb, n2Protection is lower to add dry thf15ml, and magneton stirs.It is cooled to -17 DEG C, add triethylamine (117.10 μ
L, 0.84mmol) and ethyl chloroformate (77.70 μ l, 0.82mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take
5- (4- aminophenyl) -10,15,20- Triphenylporphyrins (251.90mg, 0.40mmol) are dissolved in 10ml thf, will be above-mentioned
Filtrate adds, and reaction 24h is stirred at room temperature.Tlc (petroleum ether: ethyl acetate=2:1) monitors reaction process.After reaction completely, will
Reactant liquor is poured in frozen water, separates out precipitation, filters, and washes 3 times, obtains violet solid.Last column chromatography for separation (eluant: stone
Oily ether: ethyl acetate=3:1) obtain product 370.01mg, yield 96%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (1d) 75.14mg,
Yield 95% (synthetic route is shown in Fig. 1, characterizes collection of illustrative plates and sees Fig. 2).
Embodiment 25- { 4- [(s) -2,6- diaminourea hexanoyl amido] phenyl } -10- (4- aminophenyl) -15,20- hexichol
The preparation of base porphyrin (2d-1)
Boc-lys (boc)-oh (96.99mg, 0.28mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf7nl, magneton stirs.It is cooled to -17 DEG C, add triethylamine (40.98 μ l, 0.29mmol), and ethyl chloroformate (27.19 μ
L, 0.28mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take 5,10- bis- (4- aminophenyl) -15,20- hexichol
Base porphyrin (128.95mg, 0.20mmol) is dissolved in 10ml thf, and above-mentioned filtrate is added, and reaction 20h is stirred at room temperature.tlc
(dichloromethane: methanol: ammonia=60:1:0.6) monitors reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out
Precipitation, filters, and washes 3 times, obtains violet solid.Last column chromatography for separation (eluant: dichloromethane: ammonia=500:2.5；
Dichloromethane: methanol: ammonia=500:1:2.5) obtain product 124.48mg, yield 64%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (2d-1)
76.25mg, yield 96% (synthetic route is shown in Fig. 3, characterizes collection of illustrative plates and sees Fig. 4).
Embodiment 35,10- bis- { 4- [(s) -2,6- diaminourea hexanoyl amido] phenyl } -15,20- diphenyl porphyrin (2d-2)
Preparation
Boc-lys (boc)-oh (96.99mg, 0.28mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf7ml, magneton stirs.Be cooled to -17 DEG C, add triethylamine (40.98 μ l, 0.29mmol) and ethyl chloroformate (27.19 μ l,
0.28mmol) react 1h, generate white precipitate, filter, discard precipitation.Take 5,10- bis- (4- aminophenyl) -15,20- diphenyl
Porphyrin (51.54mg, 0.08mmol) is dissolved in 10ml thf, and above-mentioned filtrate is added, and reaction 20h is stirred at room temperature.Tlc (two
Chloromethanes: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, it is heavy to separate out
Form sediment, filter, wash 3 times, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol=60:1) obtains product
98.85mg, yield 95%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (2d-2)
67.18mg, yield 97% (synthetic route is shown in Fig. 5, characterizes collection of illustrative plates and sees Fig. 6).
Embodiment 45- { 3- [(s) -2,6- diaminourea hexanoyl amido] phenyl } -15- (3- aminophenyl) -10,20- hexichol
The preparation of base porphyrin (3d-1)
Boc-lys (boc)-oh (96.99mg, 0.28mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf7ml, magneton stirs.Be cooled to -17 DEG C, add triethylamine (40.98 μ l, 0.29mmol) and ethyl chloroformate (27.19 μ l,
0.28mmol) react 1h, generate white precipitate, filter, discard precipitation.Take 5,10- bis- (3- aminophenyl) -15,20- diphenyl
Porphyrin (128.95mg, 0.20mmol) is dissolved in 10ml thf, and above-mentioned filtrate is added, and reaction 20h is stirred at room temperature.Tlc (two
Chloromethanes: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, it is heavy to separate out
Form sediment, filter, wash 3 times, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: ammonia=500:2.5；Two
Chloromethanes: methanol: ammonia=500:1:2.5) obtain product 136.15mg, yield 70%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (3d-1)
73.86mg, yield 93% (synthetic route is shown in Fig. 7, characterizes collection of illustrative plates and sees Fig. 8).
Embodiment 55,10- bis- { 3- [(s) -2,6 diaminourea hexanoyl amidos] phenyl } -15,20- diphenyl porphyrin (3d-2)
Preparation
Boc-lys (boc)-oh (96.99mg, 0.28mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf7ml, magneton stirs.Be cooled to -17 DEG C, add triethylamine (40.98 μ l, 0.29mmol) and ethyl chloroformate (27.19 μ l,
0.28mmol) react 1h, generate white precipitate, filter, discard precipitation.Take 5,10- bis- (3- aminophenyl) -15,20- diphenyl
Porphyrin (51.54mg, 0.08mmol) is dissolved in 10ml thf, and above-mentioned filtrate is added, and reaction 20h is stirred at room temperature.Tlc (two
Chloromethanes: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, it is heavy to separate out
Form sediment, filter, wash 3 times, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol=60:1) obtains product
96.77mg, yield 93%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (3d-2)
65.80nng, yield 95% (synthetic route is shown in Fig. 9, characterizes collection of illustrative plates and sees Figure 10).
Embodiment 65- { 4- [(s) -2,6- diaminourea hexanoyl amido] phenyl } -10,15,20- three (4- aminophenyl) porphyrin
(4d-1) preparation
Boc-lys (boc)-oh (519.63mg, 1.50mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf20ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (219.50 μ l, 1.57mmol) and ethyl chloroformate (145.60
μ l, 1.53mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take to tetramino tetraphenylporphyrin (1.012g,
1.50mmol) it is dissolved in 30mlthf, above-mentioned filtrate is added, reaction 14h is stirred at room temperature.Tlc (dichloromethane: methanol: ammonia
Water=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3
Secondary, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=80:1:0.4) obtains product
676.68mg, yield 45%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (4d-1)
75.24mg, yield 94% (synthetic route is shown in Figure 11, characterizes collection of illustrative plates and sees Figure 12).
Embodiment 75,10- bis- { 4- [(s) -2,6-- diaminourea hexanoyl amido] phenyl } -15,20- bis- (4- aminophenyl)
The preparation of porphyrin (4d-2)
Boc-lys (boe)-oh (519.63mg, 1.50mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf20ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (219.50 μ l, 1.57mmol) and ethyl chloroformate (145.60
μ l, 1.53mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take to tetramino tetraphenylporphyrin (505.72mg,
0.75mmol) it is dissolved in 15ml thf, above-mentioned filtrate is added, reaction 14h is stirred at room temperature.Tlc (dichloromethane: methanol: ammonia
Water=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3
Secondary, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=60:1:0.3) obtains product
538.93mg, yield 54%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (4d-2)
66.46mg, yield 95% (synthetic route is shown in Figure 13, characterizes collection of illustrative plates and sees Figure 14).
Embodiment 85,10,15- tri- { 4- [(s) -2,6- diaminourea hexanoyl amido] phenyl } -20- (4- aminophenyl) porphyrin
(4d-3) preparation
Boc-lys (boc)-oh (519.63mg, 1.50mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf20ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (219.50 μ l, 1.57mmol) and ethyl chloroformate (145.60
μ l, 1.53mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take to tetramino tetraphenylporphyrin (337.15mg,
0.50mmol) it is dissolved in 15mlthf, above-mentioned filtrate is added, reaction 14h is stirred at room temperature.Tlc (dichloromethane: methanol: ammonia
Water=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3
Secondary, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=40:1:0.3) obtains product
580.61mg, yield 70%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (4d-3)
57.43mg, yield 90% (synthetic route is shown in Figure 15, characterizes collection of illustrative plates and sees Figure 16).
Embodiment 95,10, the preparation of 15,20- tetra- { 4- [(s) -2,6- diaminourea hexanoyl amido] phenyl } porphyrin (4d-4)
Boc-lys (boc)-oh (467.67mg, 1.35mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf20ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (197.60 μ l, 1.42mmol) and ethyl chloroformate (131.10
μ l, 1.38mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take tetramino porphyrin (202.40mg, 0.30mmo1)
It is dissolved in 15ml thf, above-mentioned filtrate is added, reaction 14h is stirred at room temperature.Tlc (dichloromethane: methanol: ammonia=60:1:
0.6) monitor reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3 times, obtain purple
Solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=30:1:0.4) obtains product 596.13mg, yield
93%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (4d-4)
51.96mg, yield 87% (synthetic route is shown in Figure 17, characterizes collection of illustrative plates and sees Figure 18).
Embodiment 105- { 2- [(s) -2,6- diaminourea amide base] phenyl } -10,15,20- three (2- aminophenyl) porphin
The preparation of quinoline (4d-5)
Boc-lys (boc)-oh (519.63mg, 1.50mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf20ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (219.50 μ l, 1.58mmol) and ethyl chloroformate (145.60
μ l, 1.53mmol) reaction 1h, generate white precipitate, filter, discard precipitation.Take adjacent tetramino tetraphenylporphyrin (1.01g,
1.50mmol) it is dissolved in 30mlthf, above-mentioned filtrate is added, reaction 14h is stirred at room temperature.Tlc (dichloromethane: methanol: ammonia
Water=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3
Secondary, obtain violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=80:1:0.4) obtains product
679.52mg, yield 47%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (4d-5)
70.21mg, yield 90% (synthetic route is shown in Figure 19).
Embodiment 115- { 4- [(s) -2- amino -3- (4- imidazole radicals) propionamido-] phenyl } -10,15,20- triphenyl porphin
The preparation of quinoline (5d)
Boc-his (boc)-oh (284.32mg, 0.8mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf15ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (117.10 μ μ l, 0.84mmol) and ethyl chloroformate (77.70
μ l, 0.82mmol) reaction 3h, generate white precipitate, filter, discard precipitation.Take 5- (4 aminophenyl) -10,15,20- triphenyl
Porphyrin (188.80mg, 0.30mmol) is dissolved in 5ml thf, and above-mentioned filtrate is added, and reaction 24h is stirred at room temperature.Tlc (two
Chloromethanes: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, it is heavy to separate out
Form sediment, filter, wash 3 times, obtain violet solid.Last column chromatography for separation (eluant: petroleum ether: ethyl acetate=10:1) must be produced
Thing 231.94mg, yield 80%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (5d) 67.43mg,
Yield 85% (synthetic route is shown in Figure 20, characterizes collection of illustrative plates and sees Figure 21).
Embodiment 125- { 4- [(s) -2- amino -2- amino -5- guanidine radicals valeryl amido] phenyl } -10,15,20- triphenyl
The preparation of porphyrin (6d)
By (s) -5- [2,3- bis- (tertbutyloxycarbonyl) guanidine radicals] -2- (t-butoxycarbonyl amino) valeric acid (boc-arg
(boc)2- oh) (379.60mg, 0.80mmol) be placed in reaction bulb, n2Protection is lower to add dry thf15ml, and magneton stirs.
It is cooled to -17 DEG C, add triethylamine (117.10 μ l, 0.84mmol) and ethyl chloroformate (77.70 μ l, 0.82mmol) reaction
1.5h, generates white precipitate, filters, discards precipitation.Take 5- (4 aminophenyl) -10,15,20- Triphenylporphyrins (251.90mg,
0.40mmol) it is dissolved in 5ml thf, above-mentioned filtrate is added, reaction 24h is stirred at room temperature.Tlc (petroleum ether: ethyl acetate=
5:1) monitor reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, filter, wash 3 times, obtain purple
Solid.Last column chromatography for separation (eluant: petroleum ether: ethyl acetate=5:1) obtains product 399.47mg, yield 92%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (6d) 66.56mg,
Yield 92% (synthetic route is shown in Figure 22, characterizes collection of illustrative plates and sees Figure 23).
Embodiment 135- { 4- [(s) -2- amino -3- (4- imidazole radicals) propionamido-] phenyl } -10,15,20- three (4- ammonia
Base phenyl) porphyrin (7d) preparation
Boc-his (boc)-oh (284.32mg, 0.80mmol) is placed in reaction bulb, n2 protection lower addition drying
Thf15ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (117.10 μ l, 0.84mmol) and ethyl chloroformate (77.70 μ
L, 0.82mmol) reaction 3h, generate white precipitate, filter, discard precipitation.Take 5,10,15,20- tetra- (4- aminophenyl) porphyrin
(269.72mg, 0.40mmol) is dissolved in 5ml thf, and above-mentioned filtrate is added, and reaction 24h is stirred at room temperature.Tlc (dichloromethane
Alkane: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separate out precipitation, mistake
Filter, washes 3 times, obtains violet solid.Last column chromatography for separation (eluant: dichloromethane: methanol: ammonia=30:1:0.15)
Obtain product 141.60mg, yield 35%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separates out purple precipitation,
Filter, wash 3 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (7d) 72.19mg, yield
90% (synthetic route is shown in Figure 24, characterizes collection of illustrative plates and sees Figure 25).
Embodiment 145- { 4- [(s) -2- amino -2- amino -5- guanidine radicals valeryl amido] phenyl } -10,15,20- three (4- ammonia
Base phenyl) porphyrin (8d) preparation
By boc-arg (boc)2- oh (379.60mg, 0.80mmol) is placed in reaction bulb, n2Protection lower addition drying
Thf15ml, magneton stirs.It is cooled to -17 DEG C, add triethylamine (117.10 μ l, 0.84mmol) and ethyl chloroformate (77.70 μ
L, 0.82mmol) reaction 1.5h, generate white precipitate, filter, discard precipitation.Take 5,10,15,20- tetra- (4- aminophenyl) porphin
Quinoline (384.35mg, 0.57mmol) is dissolved in 5ml thf, and above-mentioned filtrate is added, and reaction 24h is stirred at room temperature.Tlc (dichloro
Methane: methanol: ammonia=60:1:0.6) monitoring reaction process.After reaction completely, reactant liquor is poured in frozen water, separates out precipitation,
Filter, wash 3 times, obtain violet solid.Last column chromatography for separation (eluant: petroleum ether: ethyl acetate=2:1) obtains product
257.77mg, yield 40%.
The ch that the 100.00mg sample 10ml that above-mentioned steps are obtained is dried2cl2Dissolving, is slowly added dropwise trifluoroacetic acid
10ml, room temperature reaction 30min.Rotation remove solvent, add absolute ether, generate greenish precipitate, filter, 30ml dichloromethane and
The each washing of 30ml absolute ether 3 times.With 20ml distilled water, green precipitate is dissolved again, ammonia adjusts ph7-8, separate out purple and sink
Form sediment, filter, wash 2 times, column chromatography for separation obtains basic amino acid and modifies amino tetraphenylporphyrin compound (8d) 66.84mg,
Yield 91% (synthetic route is shown in Figure 26, characterizes collection of illustrative plates and sees Figure 27).
The external of amino tetraphenylporphyrin compound modified by embodiment 15 embodiment of the present invention 1-14 gained basic amino acid
The antibacterial evaluation of light power (list of references: antimicrobagents chemother1995,39 (5): 1169), walk including following
Rapid:
(1) experimental strain
This experiment has selected following 3 kinds of common human body cause illness's normal bacterial bacterial strains as screening object, bacterial isolateses by
Beijing 304 hospital provides:
Methicillin-resistant staphylococcus aureus (mrsa) are by Beijing 304 hospital clinical separation and Extraction
Pseudomonas aeruginosa (p.aeru) atcc27853
Escherichia coli (e.coli) atcc25922
(2) experimental technique
Bacteria suspension is prepared: with aseptic manipulation, after taking 3 kinds of lyophilizing standard strains to recover room temperature, with plate streak, difference
Straight line is drawn on 3 lb solid medium flat boards, 37 DEG C of culture 18h, according still further to fluid medium inocalation method, with inoculating loop difference
Dip strain subcultivation in 3 lb fluid mediums respectively containing 5ml, 35 DEG C of culture 16h on the shaking table of 180rpm, then by this bacterium
Liquid is diluted to 1 × 106Cfu/ml is standby.
Drug solution preparing: take embodiment of the present invention 1-14 gained basic amino acid to modify amino tetraphenylporphyrin compound and be dissolved in
Dimethyl sulfoxide, is made into the medicine storing liquid of 5mm, preserves at -20 DEG C, presses doubling dilution with lb fluid medium before experiment
Medicine is configured to the medicine of 500,250,125,62.5,31.25,15.63,7.81,3.91,1.96 μm of concentration.
A series of inoculation: draw 500 μ l medicinal liquids and be individually placed in test tubes, put into the bacterium solution having diluted in each test tube
(106Cfu/ml) (blank group is 1000 μ l lb fluid mediums to 500 μ l, and growth control group adds for 500 μ l lb fluid mediums
500 μ l bacteria suspensions), after mixing, 30min is secretly incubated on the shaking table of 180rpm, take out to be placed in and irradiate under laser (650nm, 2a)
30min, cultivates 24h after irradiation in camera bellows, takes out the muddy degree observing mattress liquid, and first medicine muddy reduction is dense
Spend for minimal inhibitory concentration (mic).Again each bacterium solution is carried out coated plate, be incubated 24h in camera bellows, observe bacterium colony in each culture dish
Growing state, first culture dish does not have the drug level that bacterium colony generates be minimum bactericidal concentration (mbc).
(3) experimental result
Ex-vivo photodynamic antibacterial experiment the results are shown in Table 1.
Above-mentioned test result indicate that, the basic amino acid of the present invention is modified amino tetraphenylporphyrin compound and is had preferably
Light power antibacterial activity, compound 2d-2, the antibacterial activity of 3d-2,4d-3 is suitable with positive control drug carbenicillin, compound
The light power antibacterial activity of 4d-2,4d-4 is better than comparison medicine；The antibacterial activity of wherein compound 4d-4 is especially prominent, to selected resistance to
Methicillin staphylococcus aureuses, bacillus pyocyaneus and colibacillary smooth power minimal inhibitory concentration are respectively 3.91,7.81,
1.95μm.The external light of amino tetraphenylporphyrin compound modified by embodiment 16 embodiment of the present invention 1-14 gained basic amino acid
Power antitumor is evaluated, and comprises the steps:
(1) the human cervical carcinoma cell hela being in growth logarithmic (log) phase cultivating conventional culture methods, is disappeared with trypsin
Change, so that attached cell is come off, be made into suspension with 1640 culture medium containing 10% hyclone, be seeded in 96 orifice plates and cultivate, 1 ×
104Individual cells/well, puts co2In incubator, incubation 24h makes cell attachment.
(2) incline culture fluid, and administration group adds a series of medicine culture fluid 100 of the increasing concen-trations pressing multiple proportion preparation
μ l, concentration is followed successively by 1.25,2.5,5,10,20 μm, matched group with culture fluid alternatives to medication solution, 4 secondary orifices of each concentration,
co2It is incubated 24h in incubator.
Mic the and mbc (μ of the ex-vivo photodynamic antibacterial experiment of amino tetraphenylporphyrin compound modified by table 1 basic amino acid
m)
(3) laser with wavelength as 650nm is irradiated, and energy density is 6j/cm2, irradiation time 20min.
(4) after irradiation terminates, in incubator, continue incubation 24h, every hole adds 50 μ l mtt (1mg/ml), continues culture
4h.Incline culture fluid, and every hole adds 150 μ l dmso dissolving color crystallizations.
(5) each hole absorbance value at 490nm wavelength is detected on microplate reader, using no compound incubation culture cell as
Blank, calculates medium effective concentration (ic with reed-muench method50, it is shown in Table 2).
Test result indicate that, the basic amino acid modification amino tetraphenylporphyrin compound of the present invention has preferable light and moves
Resist tumor promotion strenuously；The anti-tumor activity of wherein compound 3d-1,3d-2,4d-1,4d-2,4d-5 is especially prominent, to people's cervix uteri
The light power half-inhibition concentration of cancerous cell hela is respectively 0.71,0.42,0.58,0.82,0.62 μm.
Ex-vivo photodynamic anti-tumor activity (the ic of amino tetraphenylporphyrin compound modified by table 2 basic amino acid50, μm)
Claims (2)
1. amino tetraphenylporphyrin compound modified by a kind of basic amino acid, it is characterized in that having a structure in which
Wherein r1=r2=r3=r4=-nh-x
2. application in preparing light power antibacterials for the amino tetraphenylporphyrin compound modified by a kind of basic amino acid, described
Basic amino acid modify amino tetraphenylporphyrin compound have a structure in which
Wherein r1=-nh-x, r2=h or-nh-x, r3=h or-nh-x, r4=h or-nh-x,
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| Synthesis and cellular localization of porphyrinic pigments;Sareh, Sarah et al;《Proceedings of SPIE》;20091231;Figure 1、 Introduction * |
| Synthesis and characterization of positively charged porphyrin-peptide conjugates;Sibrian-Vazquez et al.;《Bioconjugate Chemistry》;20051231;第16卷(第4期);摘要，Introduction，第853、857-859页，第857页Scheme 1 * |
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