CN102180883A - Substituted porphyrin gold (III) compounds with anticancer activity and preparation method thereof - Google Patents
Substituted porphyrin gold (III) compounds with anticancer activity and preparation method thereof Download PDFInfo
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Abstract
The invention discloses substituted porphyrin gold (III) compounds with anticancer activity and a preparation method thereof, belonging to the technical field of medicament preparation. The preparation method comprises the following steps of: coordinating substituted tetraphenylporphyrin and gold to generate a substituted tetraphenyl porphyrin gold (III) compound; and introducing a targeting group onto a porphyrin ring to enhance the targeting selectivity of porphyrin gold, lower the toxicity of the porphyrin gold, further improve the performance of the porphyrin gold (III) compound and preserve or enhance the anticancer activity of the porphyrin gold (III) compound. As proved by in-vitro detection data of an S180 cell, the compound synthesized with the method has a remarkable suppressing function, the highest suppression ratio up to 92.863 percent higher than that of tetraphenyl porphyrin gold (III) serving as a lead compound and a weak suppressing function on normal cells. The preparation method is scientific and reasonable; and the prepared substituted porphyrin gold (III) compounds have high anticancer activity, a small toxic or side effect and a simple, convenient, and practical preparation process, and is suitable for industrial mass production.
Description
Technical field
The invention discloses replacement porphyrin gold (III) compounds with antitumour activity and preparation method thereof, belong to field of medicine preparing technology.
Background technology
Cancer is the high common disease of present lethality rate, and its clinical treatment means are mainly operation, radiotherapy and chemotherapy.In antineoplastic chemotherapy medicine, some widespread use clinically of precious metal coordination compound, for example cis-platinums.But the same with most of chemotherapeutics, the target selectivity of cis-platinum is relatively poor, also injures the normal cell of body in kill cancer cell, shows bigger toxicity.
Au (III) and Pt (II) are d
8Electronic configuration, the four-coordination compound of Au (III) and the two dimensional structure of cis-platinum are similar, therefore infer that Au (III) class title complex may have and the similar antitumour activity of cis-platinum.Existing studies show that, tetraphenylporphyrin gold vitro culture to the various human cancerous cell line (as cancer cell of oral cavity KB-3-1, cervical cancer cell HeLa, leukemia HL-60, nasopharyngeal carcinoma cell SUNE1, liver cancer cell HepG2 etc.) all have higher restraining effect [Marcon, G.; Carotti, S.; Corronnello, W.et al.J.Med.Chem.2002,45,1672-1677; Messori, L.; Abbate, F.et al.J.Med.Chem.2000,43,35-41; Guo, Z.; Sadler, P.J.Angew.Chem.Int.Ed.1999,38,1512; Che, C.M.; Sun, R.W.Y.; Yu, W.Y.et al.Chem.Commun.2003,1718-1719; Wang, Y; He, Q.Y; Sun, R.W.Y.et al.Eur.J.Pharmacol.2007,554 (2-3), 113-122; Wang, Y.; He, Q.Y.; Che, C.M.et al.Proteomics.2006,6 (1), 131-142; Wang, Y; He, Q.Y.; Sun, R.W.Y.et al.Cancer Res.2005,65 (24), 11553-11564.], and antitumour activity is better than cis-platinum.Yet the tetraphenylporphyrin gold is also relatively poor to the target selectivity of cancer cells, and toxicity is bigger, thereby the distance between its experimental study and the clinical application is also very big.Therefore, carry out chemically modified, make this metalloid coordination compound have ideal antitumour activity and lower toxic side effect, then become the technological difficulties that the synthetic field of medicine is captured.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, replacement porphyrin gold (III) compounds with antitumour activity and preparation method thereof is provided.
First purpose of the present invention is achieved through the following technical solutions, and has replacement porphyrin gold (III) compounds of antitumour activity, and its general formula is:
R ' is H or CO in the formula
2CH
3R " is OCH
3Or CO
2CH
3Or NO
2X is C or N.
Described R ' is H; R " is CO
2CH
3Or OCH
3X is C or N.
Described R ' is H; R " is CO
2CH
3X is C.
Second purpose of the present invention is achieved through the following technical solutions, preparation method with replacement porphyrin gold (III) compounds of antitumour activity, it is characterized in that, described compound is to replace porphyrin as part, in the acetic acid solution system,, carry out ion-exchange by lithium chloride then and obtain with the potassium chloraurate reaction; Described replacement porphyrin is 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin or 5,10,15,20-four (4-methoxycarbonyl) phenyl porphyrin or 5-(4-methoxycarbonyl) phenyl-10,15,20-triphenyl porphyrin compound or 5-(4-nitro) phenyl-10,15,20-triphenyl porphyrin compound or 5-(4-pyridyl)-10,15,20-triphenyl porphyrin compound.
The synthetic reaction equation that replaces porphyrin:
Reagent and reaction conditions, productive rate in the formula: propionic acid, backflow 2-4h.The product productive rate is 6.5-25%.
Replacement porphyrin gold (III) compounds preparation feedback equation with antitumour activity:
Reagent in the formula: (1) KAuCl
4, NaOAc, HOAc; (2) LiCl.The product productive rate is 40.2-95.5%.
Described preparation method may further comprise the steps:
(1) be 1 with mol ratio: the glacial acetic acid that the replacement porphyrin of 2.8-3.2: 10-14, potassium chloraurate, sodium acetate and corresponding every mmole replace porphyrin 300-610ml adds in the reaction vessel successively, and at reaction vessel internal reflux 3-4h, TLC monitors to reacting completely;
(2) steam the acetate that removes in step (1) reaction solution through rotatory evaporator and obtain the purple solid, the purple solid is dissolved in the methylene dichloride that corresponding every mmole replaces porphyrin 150-300ml, and with the distilled water wash of corresponding every mmole replacement porphyrin 600-1220ml 3-5 time;
(3) methylene dichloride in the solution behind distilled water wash in the step (2) is replaced mutually the anhydrous sodium sulfate drying of porphyrin 3.2-4kg with corresponding every mmole, filter, remove methylene dichloride through the rotatory evaporator vacuum rotary steam;
(4) with the methylene chloride eluent with the solution of removing methylene dichloride through the rotatory evaporator vacuum rotary steam in the step (3), neutral alumina or silica gel column chromatography, the second colour band product that forms is removed eluent methylene dichloride, methyl alcohol fully, use acetone until dissolved product afterwards, remove by filter insolubles;
(5) filtrate in the step (4) being added concentration is the lithium chloride solution that 0.1-0.3g/mL, corresponding every mmole replace porphyrin 100-200ml, slowly revolve steaming, treat that the purple solid occurs, and filters replacement porphyrin gold (III) compounds that the back obtains to have antitumour activity.
The present invention generates replacement tetraphenylporphyrin gold (III) compound by replacing tetraphenylporphyrin and golden coordination, introduces target group CO on porphyrin ring
2CH
3, OCH
3, NO
2, increased the target selectivity of replacement tetraphenylporphyrin gold (III) compound, in the hope of keeping or strengthen the antitumour activity of porphyrin gold (III) compound.Adopt synthetic compound of the present invention to show to have the obvious suppression effect through external detection data to the S180 cell, the highest inhibiting rate reaches 92.386%, the highest inhibiting rate that is higher than lead compound tetraphenylporphyrin gold (III) 79.375%, and little to normal cell inhibiting effect.The present invention is scientific and reasonable, and replacement porphyrin gold (III) the compounds antitumour activity of preparation is good, and toxic side effect is little, and preparation technology is simple and feasible, is fit to industrialized production.
Fig. 1 is the influence figure of the present invention to normal mouse spleen lymphocyte.
Embodiment
Further specify the present invention in conjunction with the embodiments:
The following example is used to illustrate the present invention.Plant and instrument used in following each embodiment before use should be dry, and reaction will be carried out under anhydrous condition, the logical atmosphere of reflux condensing tube upper end dress drying tube.
Embodiment 15-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin gold (G1) compound and preparation method.
In the round-bottomed flask of 250mL, add 200mL propionic acid, phenyl aldehyde (60mmol) and aubepine (20mmol), reflux.After 5.53mL (80mmol) newly steamed pyrroles and 10mL propionic acid and mix, in 30min, slowly be added drop-wise in the propionic acid solution.Continue reaction 1h then, be cooled to room temperature, separate out solid, filter, solid is used methyl alcohol, hot wash, drying respectively.The acquisition yield is 8.8% 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin (L1).
Add 5-(4-p-methoxyphenyl)-10,15 in the 50mL flask, 20-triphenyl porphyrin (L1) (0.025mmol), potassium chloraurate (0.07-0.08mmol), sodium acetate (0.25-0.35mmol) and 7.5-15.25mL glacial acetic acid, conventional reflux 3-4h.The TLC monitoring is to reacting completely.Steaming removes acetate and obtains the purple solid in the rotatory evaporator.The purple solid is dissolved in the 3.75-7.5mL methylene dichloride, and with 15-30.5mL distilled water wash 3-5 time.Methylene dichloride 80-100g anhydrous sodium sulfate drying filters.Revolve in the rotatory evaporator to steam and remove methylene dichloride.With the methylene chloride is eluent, and neutral alumina or silicagel column adopt conventional chromatography and drip washing, further refined product.First colour band is unreacted raw material, and saffron second colour band is the product of wanting.The saffron second colour band product is placed rotatory evaporator, remove fully behind eluent methylene dichloride, the methyl alcohol with minimum acetone solution product, remove by filter insolubles, filtrate adds the aqueous solution (concentration is 1g-3gLiCl/10mL distilled water) of 2.5-5mL lithium chloride.Slowly revolve steaming, promptly have the purple solid to occur, filter, obtaining yield is the chlorination 5-(4-p-methoxyphenyl)-10,15 of 94.2-95.5%, 20-triphenyl porphyrin gold compound (G1).mp?156-158℃；
1HNMR(600MHz，CDCl
3)，δ(ppm)：4.13(s，3H)，7.40(d，J＝8.4Hz，2H)，7.86-7.92(m，9H)，8.16(d，J＝8.4Hz，2H)，8.24(d，J＝8.4Hz，6H)，9.28(d，J＝7.2Hz，6H)，9.34(d，J＝5.4Hz，2H)；IR(KBr)：υ2922(s)，2856(w)，1737(w)，1612(w)，1453(w)，1368(w)，1251(w)，1176(w)，1081(w)，1027(w)，806(w)，756(w)，705(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?408，520；MS：839.9(M+1-Cl-，100％)。
In the round-bottomed flask of 250mL, add 200mL propionic acid and 4-methoxycarbonyl phenyl aldehyde (80mmol), be heated to backflow.After 5.53mL (80mmol) newly steamed pyrroles and 10mL propionic acid and mix, in 30min, slowly be added drop-wise in the propionic acid solution.Continue reaction 1h then, be cooled to room temperature, separate out solid, filter, solid is used methyl alcohol, hot wash, drying respectively.Obtain yield and be 22.0% 5,10,15,20-four (4-methoxycarbonyl) phenyl porphyrin (L2): mp＞250 ℃;
1H NMR (600MHz, CDCl
3), δ (ppm) :-2.79 (s, 2H, inner-NH), 4.11 (s, 12H ,-COOCH
3), 8.29 (d, J=7.8Hz, 8H, Ph-CH), 8.44 (d, J=7.8Hz, 8H, Ph-CH), 8.81 (s, 8H, Por-CH); IR (KBr): υ 3425 (m), 2919 (w), 1724 (s), 1607 (w), 1435 (w), 1383 (w), 1277 (m), 1108 (m), 965 (w), 803 (w), 762 (w) cm
-1UV-Vis (CH
2Cl
2)/nm 417,515,549,588, and 645.
Use the method for embodiment 1, with 5,10,15,20-four (4-methoxycarbonyl) phenyl porphyrin (L2) replaces 5-(4-is to the oxygen aminomethyl phenyl)-10,15,20-triphenyl porphyrin (L1) participates in reaction, and obtaining yield is the chlorination 5,10 of 64.5-66.9%, 15,20-four (4-methoxycarbonyl) phenyl porphyrin gold (G2).mp＞250℃；
1HNMR(600MHz，CDCl
3)，δ(ppm)：4.13(s，12H，-COOCH
3)，8.36(d，J＝7.8Hz，8H，Ph-CH)，8.52(d，J＝7.8Hz，8H，Ph-CH)，9.18(s，8H，Por-CH)；IR(KBr)：υ3433(m)，2923(m)，2856(w)，1717(s)，1609(w)，1436(w)，1278(s)，1185(w)，1107(m)，1024(m)，808(w)，762(w)，708(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?408，519；MS：1041.8(M+1-Cl-，100％)。
Embodiment 3 chlorination 5-(4-methoxycarbonyl) phenyl-10,15,20-triphenyl porphyrin gold (G3) compound and preparation method.
The method of use embodiment 1 replaces aubepine (20mmol) to participate in reaction with 4-methoxycarbonyl phenyl aldehyde (20mmol), and the acquisition yield is 9.0% 5-(4-methoxycarbonyl) phenyl-10,15,20-triphenyl porphyrin compound (L3).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：-2.79(s，2H，inner-NH)，4.11(s，3H，-COOCH
3)，7.74-7.79(m，9H，Ph-CH)，8.21(d，J＝6.6Hz，6H，Ph-CH)，8.31(d，J＝7.8Hz，2H，Ph-CH)，8.44(d，J＝7.8Hz，2H，Ph-CH)，8.79(d，J＝4.2Hz，2H，Por-CH)，8.85(s，6H，Por-CH)；IR(KBr)：υ3442(s)，3319(w)，2924(w)，2853(w)，1812(m)，1722(s)，1604(w)，1472(w)，1437(w)，1394(w)，1353(w)，1279(s)，1182(w)，1106(w)，800(m)，739(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?416，513，548，589，646。
Use the method for embodiment 1, with 5-(4-methoxycarbonyl) phenyl-10,15,20-triphenyl porphyrin compound (L3) replaces 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin (L1) participates in reaction, and obtaining yield is chlorination 5-(4-methoxycarbonyl) phenyl-10 of 81.5-83%, 15,20-triphenyl porphyrin gold (G3).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：4.13(s，3H，-COOCH
3)，7.82-7.88(m，9H，Ph-CH)，8.30(s，6H，Ph-CH)，8..42(d，J＝8.4Hz，2H，Ph-CH)，8.51(d，J＝7.2Hz，2H，Ph-CH)，9.19(s，2H，Por-CH)，9.26-9.27(m，6H，Por-CH)；IR(KBr)：υ＝3414(w)，2921(s)，2852(m)，1737(w)，1601(w)，1498(w)，1460(w)，1357(w)，1242(m)，1176(w)，1079(w)，1026(m)，802(w)，756(w)，702(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?410，521；MS：868.1(M+1-Cl-，100％)。
The method of use embodiment 1 replaces aubepine (20mmol) to participate in reaction with 4-nitrobenzaldehyde (20mmol), and the acquisition yield is 8.5% 5-(4-nitro) phenyl-10,15,20-triphenyl porphyrin compound (L4).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：-2.79(s，2H，inner-NH)，7.75-7.81(m，9H，Ph-CH)，8.21(d，J＝7.2Hz，6H，Ph-CH)，8.40(d，J＝8.4Hz，2H，Ph-CH)，8.64(d，J＝8.4Hz，2H，Ph-CH)，8.74(d，J＝4.2Hz，2H，Por-CH)，8.86-8.90(m，6H，Por-CH)；IR(KBr)：υ3446(s)，2918(w)，2850(w)，1596(w)，1517(w)，1472(w)，1392(w)，1345(m)，1073(w)，840(w)，798(m)，706(m)cm
-1；UV-Vis(CH
2Cl
2)/nm?418，514，549，588，645。
Use the method for embodiment 1, with 5-(4-nitro) phenyl-10,15,20-triphenyl porphyrin compound (L4) replaces 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin (L1) participates in reaction, and obtaining yield is chlorination 5-(4-nitro) phenyl-10 of 40.2-42.6%, 15,20-triphenyl porphyrin gold (G4).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：7.78-7.82(m，9H，Ph-CH)，8.18(s，6H，Ph-CH)，8.47(s，2H，Ph-CH)，8.65(s，2H，Ph-CH)，9.06(s，2H，Ph-CH)，9.18(d，J＝8.4Hz，6H，Por-CH)；IR(KBr)：υ3438(s)，2922(m)，2856(w)，1733(w)，1629(w)，1517(w)，1452(w)，1346(w)，1086(w)，1028(w)，803(w)，756(w)，703(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?408，520；MS：855.1(M+1-Cl-，100％)。
Embodiment 5 chlorination 5-(4-pyridyl)-10,15,20-triphenyl porphyrin gold (G5) compound and preparation method.
The method of use embodiment 1 replaces aubepine (20mmol) to participate in reaction with 4-pyridylaldehyde (20mmol), and the acquisition yield is 6.5% 5-(4-pyridyl)-10,15,20-triphenyl porphyrin compound (L5).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：-2.82(s，2H，inner-NH)，7.75-7.80(m，9H，Ph-CH)，8.17(d，J＝5.4Hz，2H，Ph-CH)，8.21(d，J＝6.6Hz，6H，Ph-CH)，8.79(d，J＝4.2Hz，2H，Ph-CH)，8.86-8.90(m，6H，Por-CH)，9.03(s，2H，Por-CH)；IR(KBr)：υ3446(s)，1634(w)，1590(w)，1473(w)，1396(w)，1351(w)，1070(w)，970(w)，798(m)，710(m)，657(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?416，513，548，586，644。
Use the method for embodiment 1, with 5-(4-pyridyl)-10,15,20-triphenyl porphyrin compound (L5) replaces 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin (L1) participates in reaction, and obtaining yield is the chlorination 5-(4-pyridyl)-10 of 81.5-82.2%, 15,20-triphenyl porphyrin gold (G5).mp＞250℃；
1H?NMR(CDCl
3，600MHz)，δ(ppm)：7.84-7.91(m，9H，Ph-CH)，8.25(d，J＝7.8Hz，8H，Ph-CH)，9.14(d，J＝4.2Hz，2H，Ph-CH)，9.18(d，J＝5.4Hz，2H，Por-CH)，9.26(s，4H，Por-CH)，9.29(s，2H，Por-CH)；IR(KBr)：υ3437(s)，2925(m)，2859(w)，1629(w)，1447(w)，1368(w)，1083(w)，1031(w)，804(w)，759(w)，706(w)cm
-1；UV-Vis(CH
2Cl
2)/nm?407，519；MS：811.2(M+1-Cl-，100％)。
Its high-efficiency low-toxicity characteristic sees following explanation for details:
1. to the inhibiting rate height of tumour cell, half-inhibition concentration is little
Get the S180 cell (Chinese Academy of Sciences's Shanghai cell research provides) that external continuous passage is in logarithmic phase, adjust cell count to 1 * 10 with RPMI1640 (the Gbico company product) nutrient solution that contains 10% newborn calf serum behind the centrifuge washing
5/ mL.Get this cell suspension 100 μ L, add 96 well culture plates, the every hole of dosing group adds the testing sample 100 μ L of different concns, the blank group adds RPMI-1640 100 μ L, positive controls adds the cis-platinum solution 100 μ L of different concns, and each concentration is established 3 multiple holes, and culture plate is placed 5%CO
2, 37 ℃ of saturated humidities incubator in cultivate 48h.4h sucking-off 100 μ L supernatants from each hole discard before cultivating end, add MTT10 μ L (final concentration 5mg/mL, MTT is a sigma company product), after continuing to cultivate 4h, add 100 μ L acidifying Virahol termination reactions, vibration 10min, with the OD value of microplate reader in each hole of mensuration, 570nm place, the height of OD value is directly proportional with viable count.By formula " inhibiting rate=(1-medicine hole OD value/control wells OD value) * 100% " calculates the external inhibiting rate to S180 cell proliferation of test-compound, and calculation of half inhibitory concentration IC
50The results are shown in Table 1.
Table 1 pair S180 cells in vitro inhibition of proliferation effect
Table 1 result shows, replaces porphyrin gold (III) compounds G1, G3 and G5 the S180 cell is had the obvious suppression effect, wherein the IC of G1 and G3
50All less than lead compound (G0), G3 is 92.386% to the highest inhibiting rate of tumour cell, is higher than the highest inhibiting rate 79.375% of lead compound, and G2, G4 to the effect relatively of S180 cell inhibiting a little less than.
2. the toxicity to normal mouse spleen lymphocyte is little
Prepare ICR mouse spleen lymphocyte suspension according to a conventional method, regulating cell concn is 1 * 10
7/ mL.Get this cell suspension 100 μ L, add 96 well culture plates, the every hole of dosing group adds the testing sample 100 μ L of different concns, the blank group adds 1640 (Gbico company product) nutrient solution, 100 μ L, positive controls adds the cis-platinum solution 100 μ L of different concns, each concentration is established 3 multiple holes, places the incubator of 5%CO2,37 ℃ of saturated humidities to cultivate 48h culture plate.4h sucking-off 100 μ L supernatants from each hole discard before cultivating end, add MTT10 μ L (final concentration 5mg/mL, MTT is a sigma company product), after continuing to cultivate 4h, add 100 μ L acidifying Virahol termination reactions, vibration 10min is with the OD value of microplate reader in each hole of mensuration, 570nm place, the height of OD value becomes positive correlation with the quantity of viable cell, and Normocellular toxicity is become negative correlation.The result as shown in Figure 1.
Fig. 1 result shows: test-compound all has certain toxicity to normal mouse spleen lymphocyte, wherein lead compound G0 toxicity is bigger, secondly be cis-platinum, the toxicity of compound G1 and G3 is less, measure in conjunction with antitumour activity, new synthetic targeting compounds selectivity is good, toxicity is low, probably becomes anticancer potential drug to show these two.
Claims (5)
1. have replacement porphyrin gold (III) compounds of antitumour activity, its general formula is:
R ' is H or CO in the formula
2CH
3R " is OCH
3Or CO
2CH
3Or NO
2X is C or N.
2. replacement porphyrin gold (III) compounds with antitumour activity according to claim 1 is characterized in that described R ' is H; R " is CO
2CH
3Or OCH
3X is C or N.
3. replacement porphyrin gold (III) compounds with antitumour activity according to claim 2 is characterized in that described R ' is H; R " is CO
2CH
3X is C.
4. have the preparation method of replacement porphyrin gold (III) compounds of antitumour activity, it is characterized in that, described compound with the potassium chloraurate reaction, carries out ion-exchange by lithium chloride then and obtains in the acetic acid solution system to replace porphyrin as part; Described replacement porphyrin is 5-(4-p-methoxyphenyl)-10,15,20-triphenyl porphyrin or 5,10,15,20-four (4-methoxycarbonyl) phenyl porphyrin or 5-(4-methoxycarbonyl) phenyl-10,15,20-triphenyl porphyrin compound or 5-(4-nitro) phenyl-10,15,20-triphenyl porphyrin compound or 5-(4-pyridyl)-10,15,20-triphenyl porphyrin compound.
5. the preparation method with replacement porphyrin gold (III) compounds of antitumour activity according to claim 4 is characterized in that described preparation method may further comprise the steps:
(1) be 1 with mol ratio: the glacial acetic acid that the replacement porphyrin of 2.8-3.2: 10-14, potassium chloraurate, sodium acetate and corresponding every mmole replace porphyrin 300-610ml adds in the reaction vessel successively, and at reaction vessel internal reflux 3-4h, TLC monitors to reacting completely;
(2) steam the acetate that removes in step (1) reaction solution through rotatory evaporator and obtain the purple solid, the purple solid is dissolved in the methylene dichloride that corresponding every mmole replaces porphyrin 150-300ml, and with the distilled water wash of corresponding every mmole replacement porphyrin 600-1220ml 3-5 time;
(3) methylene dichloride in the solution behind distilled water wash in the step (2) is replaced mutually the anhydrous sodium sulfate drying of porphyrin 3.2-4kg with corresponding every mmole, filter, remove methylene dichloride through the rotatory evaporator vacuum rotary steam;
(4) with the methylene chloride eluent with the solution of removing methylene dichloride through the rotatory evaporator vacuum rotary steam in the step (3), neutral alumina or silica gel column chromatography, the second colour band product that forms is removed eluent methylene dichloride, methyl alcohol fully, use acetone until dissolved product afterwards, remove by filter insolubles;
(5) filtrate in the step (4) being added concentration is the lithium chloride solution that 0.1-0.3g/mL, corresponding every mmole replace porphyrin 100-200ml, slowly revolve steaming, treat that the purple solid occurs, and filters replacement porphyrin gold (III) compounds that the back obtains to have antitumour activity.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017097226A1 (en) * | 2015-12-08 | 2017-06-15 | The University Of Hong Kong | Gold porphyrin-peg conjugates and methods of use |
| US11958103B2 (en) | 2018-07-09 | 2024-04-16 | Kao Corporation | Inorganic coated sand |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040063681A1 (en) * | 2002-09-16 | 2004-04-01 | Chi-Ming Che | Methods for using gold (III) complexes as anti-tumor and anti-HIV agents |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040063681A1 (en) * | 2002-09-16 | 2004-04-01 | Chi-Ming Che | Methods for using gold (III) complexes as anti-tumor and anti-HIV agents |
Non-Patent Citations (3)
| Title |
|---|
| 《Chem. Eur. J.》 20101231 Raymond Wai-Yin Sun Stable Anticancer GoldACHTUNGTRENUNG(III)-Porphyrin Complexes:Effects of Porphyrin Structure 3097 - 3113 1-5 , 第16期 * |
| RAYMOND WAI-YIN SUN: "Stable Anticancer GoldACHTUNGTRENUNG(III)–Porphyrin Complexes:Effects of Porphyrin Structure", 《CHEM. EUR. J.》 * |
| RAYMOND WAI-YIN SUN等: "In Vitro Inhibition of Human Immunodeficiency Virus Type-1 (HIV-1) Reverse Transcriptase by Gold(iii)Porphyrins", 《CHEMBIOCHEM》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017097226A1 (en) * | 2015-12-08 | 2017-06-15 | The University Of Hong Kong | Gold porphyrin-peg conjugates and methods of use |
| US11958103B2 (en) | 2018-07-09 | 2024-04-16 | Kao Corporation | Inorganic coated sand |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102180883B (en) | 2013-04-17 |
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