CN110294707A - Environmentally friendly fluoroquinolone molecule derivative preparation method - Google Patents
Environmentally friendly fluoroquinolone molecule derivative preparation method Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The present invention provides a kind of environmentally friendly fluoroquinolone molecule derivative preparation methods, belong to quinolone antibiotics technical field.This method constructs HQSAR model, carries out molecular modification to target FQs molecule using modification group, obtains FQs molecule derivant；Filter out FQs molecule derivant of the genetoxic value higher than the genetoxic value of target FQs molecule, the FQs molecule derivant for filtering out while meeting bioconcentration threshold value and degradability threshold value again finally filters out streptococcus pneumonia genetoxic and meets default streptococcus pneumonia genetoxic threshold value FQs molecule derivant.The present invention provides foundation for the characteristic (toxicity, photodegradation, biological degradability, bioconcentration) and Genotoxic Effect mechanism for more deeply probing into FQs, have found the critical sites and influencing factor for influencing FQs genetoxic, it realizes that FQs molecule is environmentally friendly and its molecular modification of the high bactericidal properties of derivative, provides completely new thinking for the molecular modification and screening of FQs.
Description
Technical field
The present invention relates to quinolone antibiotics technical fields, and in particular to a kind of environmentally friendly fluoroquinolone molecule spreads out
Biological preparation method.
Background technique
Quinolone drugs is the bactericidal properties antibacterials of a kind of artificial synthesized public skeleton structure with ketone acid, is belonged to
In acidum nalidixicum or the derivative of pyridonecarboxylic acid.With the fast development of quinolone drugs, because of its broad spectrum activity, high efficiency, safety
The features such as, it is the various most common drugs of bacterium infection for the treatment of, including upper and lower respiratory tract infection, partial skin and community obtain
Property pneumonia etc. is obtained, is had a extensive future.
1976, the DNA gyrase of the discovery Escherichia coli such as Gellert can be inhibited by acidum nalidixicum, to confirm DNA
Gyrase is the effect target molecule of quinolone drugs.Researcher generally believed that DNA gyrase was known in bacterial body at that time
Double-stranded DNA can be uniquely set to generate the topoisomerase of negative supercoiling, later with the deep discovery Topoisomerase Ⅳ of research
It is also the target site of quinolone drugs.It is generally acknowledged that type Ⅱ topoisomerase (DNA gyrase) is quinoline in gram-negative bacteria
The pharmaceutically-active major target class of promise ketone；And in gram positive bacteria, Topoisomerase Ⅳ is most of quinolone drugs
Inhibit target spot.After quinolone antibiotics enter bacterial cell, quinolone antibiotics and DNA, DNA gyrase or topoisomerase
Enzyme IV occurs reciprocation and forms a stable drug-enzyme-DNA compound, the configuration of induced enzyme and DNA change to
The function of causing enzyme that cannot bring into normal play DNA, eventually causes DNA degradation and thallus is dead.DNA gyrase and topoisomerase
IV is enzyme necessary to bacterial growth, and any enzyme is suppressed the growth retardation that will all make cell, eventually leads to cell
Death.
Quinolones is capable of two kinds of enzymes that the inhibition of selectivity is worked in DNA synthesis: topoisomerase in bacterial body
Enzyme II and IV makes bacterium that can not pass on and be suppressed, shows to disturb the duplication of DNA of bacteria, transcription and repair recombination
Genetoxic.Quinolone antibiotics have good pharmacokinetic properties and treatment effect in treatment humans and animals bacterial infection
Fruit, have a wide range of application, usage amount it is big.Quinolone medicine is a kind of important antibacterials, and usage amount is located at antibacterials
Forefront.40%~90% enters environment with feces of livestock and poultry in the form of parent or metabolism after antibiotic enters in human or animal's body.
Environmental survey discovery, quinolone antibiotics have detection in a variety of surrounding mediums such as water body, deposit, soil.Some
In water body and soil around farm, antibiotic content can reach abnormal high level.Therefore, design antibacterial activity enhancing and
Environmentally friendly novel carbostyril antibiotic is very necessary.
Summary of the invention
The purpose of the present invention is to provide a kind of environmentally friendly fluoroquinolone molecule derivative preparation methods, on solving
State technical problem present in background technique.
To achieve the goals above, this invention takes following technical solutions:
A kind of environmentally friendly fluoroquinolone molecule derivative preparation method provided by the invention, including following process step
It is rapid:
Step S110: according to the genetoxic of target FQs molecule, it is fixed that holographic elements corresponding to target FQs molecule are constructed
Measure structure-activity relationship HQSAR model；
Step S120: according to HQSAR model, molecular modification is carried out to target FQs molecule using modification group, obtains FQs
Molecule derivant；
Step S130: filtering out FQs molecule derivant of the genetoxic value higher than the genetoxic value of target FQs molecule,
As level-one FQs molecule derivant；
Step S140: it in level-one FQs molecule derivant, filters out while meeting bioconcentration threshold value and degradability threshold
The FQs molecule derivant of value, as second level FQs molecule derivant；
Step S150: it in second level FQs molecule derivant, filters out streptococcus pneumonia genetoxic and meets default pneumonia streptococcus
Bacterium genetoxic threshold value FQs molecule derivant, as three-level FQs molecule derivant to get the environmentally friendly fluoquinolone
Molecule derivant.
Preferably, the step S120 is specifically included:
According to HQSAR model corresponding to target FQs molecule, combining target FQs molecular activity contribution plot determines No. 7 originals
Sub- position is decorating site, chooses modification group for the decorating site and carries out single substitution reaction, carries out to target FQs molecule
Molecular modification；
Using 2.0 method of SYBYL-X in density functional theory, the base of the FQs molecule derivant after optimizing molecular modification
State geometry obtains FQs molecule derivant.
Preferably, the modification group be wherein, the modification group be 1- methyl piperazine, 1- ethyl -4- methyl piperazine,
In 1,3- lupetazin, 1- methyl piperidine -4- alcohol, 1,3,5- tri methyl piperazine or 1- methyl -3- cyclopropyl -4- amino piperidine
One kind.
Preferably, the bioconcentration threshold value is the logarithm of living being concentration ratio, and the degradability threshold value is half-life period
Logarithm.
Preferably, in the step S130, the streptococcus pneumonia genetoxic includes multiple with Topoisomerase Ⅳ-DNA
Close object combine amino acid classes, hydrophily, polarity, away from discrete frequency.
Preferably, using molecular docking method simulation three-level FQs molecule derivant and Topoisomerase Ⅳ-DNA compound
Combination.
Preferably, the structural formula of the target FQs molecule are as follows:
Wherein, R1、R2、R3、R4、R5Respectively represent any group.
Preferably, in the step s 120, the structural formula for obtaining 35 kinds of FQs molecule derivants is respectively as follows:
Preferably, the structural formula of the environmentally friendly fluoroquinolone molecule derivative are as follows:
The invention has the advantages that: it is easy to operate, calculate it is quick, easy to accomplish, not only can be with theoretical validation FQs molecular modification
And the feasibility of screening scheme, and can more deeply probe into characteristic (toxicity, photodegradation, biological degradability, the life of FQs
Object enriching) and Genotoxic Effect mechanism, the critical sites and influencing factor for influencing FQs genetoxic are found, realize FQs
Molecule is environmentally friendly and its molecular modification of the high bactericidal properties of derivative；In addition, provided by the invention be based on HQSAR model
The detection method R&D cycle is short, at low cost, can save a large amount of human and material resources and financial resources, is the molecular modification and screening of FQs
Provide completely new thinking.
The additional aspect of the present invention and advantage will be set forth in part in the description, these will become from the following description
Obviously, or practice through the invention is recognized.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, required use in being described below to embodiment
Attached drawing be briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for this
For the those of ordinary skill of field, without creative efforts, it can also be obtained according to these attached drawings others
Attached drawing.
Fig. 1 is environmentally friendly fluoroquinolone molecule derivative preparation method flow chart described in the embodiment of the present invention 1.
Fig. 2 is environmentally friendly fluoroquinolone molecule derivative preparation method flow chart described in the embodiment of the present invention 2.
Specific embodiment
It is exemplary below with reference to the embodiment of attached drawing description, for explaining only the invention, and cannot explain
For limitation of the present invention.
Those skilled in the art of the present technique are appreciated that unless expressly stated, singular " one " used herein, " one
It is a ", " described " and "the" may also comprise plural form.It is to be further understood that being arranged used in specification of the invention
Diction " comprising " refer to that there are the feature, integer, step, operation, element and/or modules, but it is not excluded that in the presence of or addition
Other one or more features, integer, step, operation, element, module and/or their group.
Those skilled in the art of the present technique are appreciated that unless otherwise defined, all terms used herein (including technology art
Language and scientific term) there is meaning identical with the general understanding of those of ordinary skill in fields of the present invention.Should also
Understand, those terms such as defined in the general dictionary, which should be understood that, to be had and the meaning in the context of the prior art
The consistent meaning of justice, and unless defined as here, it will not be explained in an idealized or overly formal meaning.
In order to facilitate understanding of embodiments of the present invention, further by taking specific embodiment as an example below in conjunction with attached drawing to be solved
Explanation is released, and embodiment does not constitute the restriction to the embodiment of the present invention.
Those of ordinary skill in the art are it should be understood that attached drawing is the schematic diagram of one embodiment, the portion in attached drawing
Part or device are not necessarily implemented necessary to the present invention.
Embodiment 1
As shown in Figure 1, the embodiment of the present invention 1 provides a kind of environmentally friendly fluoroquinolone molecule derivative preparation method,
Including following process step:
Step S110: according to the genetoxic of target FQs molecule, it is fixed that holographic elements corresponding to target FQs molecule are constructed
Measure structure-activity relationship HQSAR model；
Step S120: according to HQSAR model, molecular modification is carried out to target FQs molecule using modification group, obtains FQs
Molecule derivant；
Step S130: obtaining the genetoxic of FQs molecule derivant, filters out the FQs that genetoxic is higher than first threshold
Molecule derivant, as level-one FQs molecule derivant；
Step S140: it in level-one FQs molecule derivant, filters out while meeting bioconcentration threshold value and degradability threshold
The FQs molecule derivant of value, as second level FQs molecule derivant；
Step S150: it in second level FQs molecule derivant, filters out streptococcus pneumonia genetoxic and meets default pneumonia streptococcus
Bacterium genetoxic threshold value FQs molecule derivant, as three-level FQs molecule derivant to get the environmentally friendly fluoquinolone
Molecule derivant.
The step S120 is specifically included:
According to HQSAR model corresponding to target FQs molecule, combining target FQs molecular activity contribution plot determines No. 7 originals
Sub- position is decorating site, chooses modification group for the decorating site and carries out single substitution reaction, carries out to target FQs molecule
Molecular modification；
Using 2.0 method of SYBYL-X in density functional theory, the base of the FQs molecule derivant after optimizing molecular modification
State geometry obtains FQs molecule derivant.
The modification group is that wherein, the modification group is 1- methyl piperazine, 1- ethyl -4- methyl piperazine, 1,3- bis-
One in methyl piperazine, 1- methyl piperidine -4- alcohol, 1,3,5- tri methyl piperazine or 1- methyl -3- cyclopropyl -4- amino piperidine
Kind.
The bioconcentration threshold value is the logarithm of living being concentration ratio, and the degradability threshold value is the logarithm of half-life period.
In the step S130, the streptococcus pneumonia genetoxic includes in conjunction with Topoisomerase Ⅳ-DNA compound
Amino acid classes, hydrophily, polarity, away from discrete frequency.
Using the combination of molecular docking method simulation three-level FQs molecule derivant and Topoisomerase Ⅳ-DNA compound.
The structural formula of the target FQs molecule are as follows:
Wherein, R1、R2、R3、R4、R5Respectively represent any group.
In the step s 120, the structural formula of 35 kinds of FQs molecule derivants of acquisition is respectively as follows:
In the step S130, the first threshold is the genetoxic of target FQs molecule, is respectively as follows:
Amifloxacin (AMI): 8.00, Balofloxacin (BAL): 7.31, Cinoxacin (CIN): 6.52, Fleroxacin
(FLE): 6.77, Pazufloxacin (PAZ): 8.54, Rufloxacin (RUF): 6.89.
The structural formula of the environmentally friendly fluoroquinolone molecule derivative are as follows:
Embodiment 2
As shown in Fig. 2, the embodiment of the present invention 2 provides a kind of environmentally friendly FQs molecule derivant transformation screening technique, use
Spread out in obtaining corresponding to target FQs molecule, meeting specified desired target FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule
Biology.
Method described in the embodiment of the present invention 2 specifically comprises the following steps:
Step A. is according to the genetoxic of target FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule, by the side HQSAR
Method establishes the salmonella typhimurium genetoxic model of quinolone antibiotics, and HQSAR produces holographic elements description, warp
Molecular fragment analysis can show the activity contribution of the every point atom of molecule.Subsequently into step B.
Step B. HQSAR model, such as Fig. 2 according to corresponding to target FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule
It is shown, in conjunction with the active contribution plot of FQs (AMI, BAL, CIN, FLE, PAZ, RUF), determine for FQs (AMI, BAL, CIN, FLE,
PAZ, RUF) the specific site modified of molecule, selection specifies each group for target FQs molecule progress molecular modification,
Obtain each FQs to be detected (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant.
In practical application, by HQSAR model corresponding to FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule with
FQs (AMI, BAL, CIN, FLE, PAZ, RUF) activity contribution plot, determines to FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule
The specific site modified；Determine that choosing No. 7 atom sites introducing substituent groups carries out monosubstituted, 6 kinds of specified bases of selection
Group be modification group, including 1- methyl piperazine, 1- ethyl -4- methyl piperazine, 1,3- lupetazin, 1- methyl piperidine -4- alcohol,
1,3,5- tri methyl piperazine and 1- methyl -3- cyclopropyl -4- amino piperidine carry out single substitution reaction, at above-mentioned site to obtain
Obtain each FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant to be detected.
Then optimize the ground state geometry of each FQs to be detected (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant,
Each FQs to be detected (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant is updated, and enters step C；Wherein, practical application
In, using the B3LYP method in density functional theory, optimize each FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule to be detected
The ground state geometry of derivative.
Step C. by 2.0 software of SYBYL-X, using DFT method (DFT) obtain each FQs to be detected (AMI,
BAL, CIN, FLE, PAZ, RUF) the corresponding genetoxic of molecule derivant difference, subsequently into step D.
Step D. is directed to each FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant to be detected respectively first, obtains
Genetoxic corresponding to FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant to be detected, relative target FQs (AMI,
BAL, CIN, FLE, PAZ, RUF) genetoxic size variation corresponding to molecule；Then screening obtains wherein genetoxic enhancing and becomes
Change is more than each to be checked of preset threshold (AMI:8.00, BAL:7.31, CIN:6.52, FLE:6.77, PAZ:8.54, RUF:6.89)
Totally 35 kinds of FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant is surveyed, the knot of the FQs molecule derivant to be detected in 35
Structure formula is as follows:
Step E. by screened in step D obtained genetoxic enhancing variation more than preset threshold each FQs to be detected (AMI,
BAL, CIN, FLE, PAZ, RUF) molecule derivant, spreads out as each primary FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule
Biology.
Respectively be directed to each primary FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant, using bioconcentration with
Photodegradation QSAR model, which calculates, obtains bioconcentration and photodegradation corresponding to primary FQs molecule derivant, as this
POPs feature corresponding to primary FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant；Then screening obtains while expiring
Foot default bioconcentration value threshold value (AMI:-0.80, BAL:0.99, CIN:1.58, FLE:0.05, PAZ:-0.13, RUF:-
And degradability value threshold value (AMI:3.16, BAL:2.73, CIN:2.56, FLE:0.635, PAZ:2.413, RUF:1.564) 0.10)
Each primary FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant, subsequently into step F.
Screening in step E is obtained while meeting each primary of default bioconcentration and photodegradation threshold value by step F.
FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant, as each middle rank FQs (AMI, BAL, CIN, FLE, PAZ,
RUF) molecule derivant；
Pneumonia streptococcus corresponding to each middle rank FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant is obtained respectively
Bacterium genetoxic, then screening obtain meet simultaneously each advanced FQs for presetting streptococcus pneumonia genetoxic threshold value (AMI, BAL,
CIN, FLE, PAZ, RUF) totally 4 kinds of molecule derivant, chemical structural formula is as follows:
In the step F, bioconcentration parameter is logKow value, and degradability parameter is logt1/2 value, genetoxic ginseng
Number is pLOEC value, and the protein structure of the Topoisomerase Ⅳ-DNA compound in white-rot fungi and streptococcus pneumonia is originated from
Protein Data Bank (http://www.rcsb.org/pdb), PDB ID are respectively 1TZL and 4Z53.
In the step F, the corresponding pneumonia of middle rank FQs (AMI, BAL, CIN, FLE, the PAZ, RUF) molecule derivant
Streptococcus genetoxic (pLOEC) include in conjunction with Topoisomerase Ⅳ-DNA compound amino acid classes (ARG, ASN,
ASP, LEU), hydrophily, polarity, away from discrete frequency.
In the step F, it is directed to each advanced FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant respectively, uses
Molecular docking method simulates advanced FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant and Topoisomerase Ⅳ-DNA
The combination of compound.
Then screening obtain wherein meet default degradability characteristic threshold value each advanced FQs (AMI, BAL, CIN, FLE,
PAZ, RUF) molecule derivant, as each target FQs (AMI, BAL, CIN, FLE, PAZ, RUF) molecule derivant, finishing screen
It selects 4 kinds and (amplification 0.53%-70.45%), bioconcentration significant decrease is promoted to gram-negative/positive bacteria inhibitory effect
(range of decrease 10.75%-27.50%), photodegradation enhance obvious (amplification 33.70%-40.92%) and biological degradability mentions
The environmentally friendly FQs molecule derivant (being AMI derivative) of high (amplification 8.15%-47.75%).
In conclusion the method for proposition of the embodiment of the present invention is easy to operate, it is quick, easy to accomplish to calculate, can not only manage
By verifying FQs molecular modification and the feasibility of screening scheme, and it can more deeply probe into characteristic (toxicity, light degradation of FQs
Property, biological degradability, bioconcentration) and Genotoxic Effect mechanism, find the critical sites for influencing FQs genetoxic and
Influencing factor realizes that FQs molecule is environmentally friendly and its molecular modification of the high bactericidal properties of derivative；In addition, the present invention provides
It is short, at low cost based on the HQSAR model checking method R&D cycle, a large amount of human and material resources and financial resources can be saved, be FQs
Molecular modification and screening provide completely new thinking.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
In the technical scope disclosed by the present invention, any changes or substitutions that can be easily thought of by anyone skilled in the art,
It should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be with scope of protection of the claims
Subject to.
Claims (9)
1. a kind of environmentally friendly fluoroquinolone molecule derivative preparation method, which is characterized in that including following process step:
Step S110: according to the genetoxic of target FQs molecule, holographic elements Quantitative Structure corresponding to target FQs molecule is constructed
Effect relationship HQSAR model；
Step S120: according to HQSAR model, molecular modification is carried out to target FQs molecule using modification group, obtains FQs molecule
Derivative；
Step S130: filtering out FQs molecule derivant of the genetoxic value higher than the genetoxic value of target FQs molecule, as
Level-one FQs molecule derivant；
Step S140: in level-one FQs molecule derivant, filter out while meeting bioconcentration threshold value and degradability threshold value
FQs molecule derivant, as second level FQs molecule derivant；
Step S150: it in second level FQs molecule derivant, filters out streptococcus pneumonia genetoxic and meets default streptococcus pneumonia something lost
Toxicity threshold FQs molecule derivant is passed, as three-level FQs molecule derivant to get the environmentally friendly fluoroquinolone molecule
Derivative.
2. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 1, which is characterized in that described
Step S120 is specifically included:
According to HQSAR model corresponding to target FQs molecule, combining target FQs molecular activity contribution plot determines No. 7 atom positions
It is set to decorating site, modification group is chosen for the decorating site and carries out single substitution reaction, molecule is carried out to target FQs molecule
Modification；
Ground state using 2.0 method of SYBYL-X in density functional theory, the FQs molecule derivant after optimizing molecular modification is several
What structure obtains FQs molecule derivant.
3. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 2, which is characterized in that described
Modification group is that wherein, the modification group is 1- methyl piperazine, 1- ethyl -4- methyl piperazine, 1,3- lupetazin, 1- first
One of phenylpiperidines -4- alcohol, 1,3,5- tri methyl piperazine or 1- methyl -3- cyclopropyl -4- amino piperidine.
4. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 1, which is characterized in that described
Bioconcentration threshold value is the logarithm of living being concentration ratio, and the degradability threshold value is the logarithm of half-life period.
5. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 1, which is characterized in that described
In step S130, the streptococcus pneumonia genetoxic includes the amino acid kind in conjunction with Topoisomerase Ⅳ-DNA compound
Class, hydrophily, polarity, away from discrete frequency.
6. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 5, which is characterized in that use
The combination of molecular docking method simulation three-level FQs molecule derivant and Topoisomerase Ⅳ-DNA compound.
7. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 1-6, feature
It is, the structural formula of the target FQs molecule are as follows:
Wherein, R1、R2、R3、R4、R5Respectively represent any group.
8. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 7, which is characterized in that in step
In rapid S120, the structural formula for obtaining 35 kinds of FQs molecule derivants is respectively as follows:
9. environmentally friendly fluoroquinolone molecule derivative preparation method according to claim 8, which is characterized in that described
The structural formula of environmentally friendly fluoroquinolone molecule derivative are as follows:
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