Synthesis and Analgesic, · Web view6.0 Brief resume of the intended work. 6.1 Need for study. The...
Transcript of Synthesis and Analgesic, · Web view6.0 Brief resume of the intended work. 6.1 Need for study. The...
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF QUINOLINE DERIVATIVES
M. Pharm. Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560041
ByMr. Patel Niravkumar Ashokbhai B.Pharm
Under the Guidance of
Dr. S. D. JOSHI M. Pharm, Ph.D.
PROFESSOR & HEAD,
DEPT. OF PHARMACEUTICAL CHEMISTRY,
Department of Pharmaceutical Chemistry
SET’s College of Pharmacy,S. R. Nagar, Dharwad,
1
Karnataka – 580002.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE –II
PROFORMA FOR REGISTRATION OF SUBJECT DISSERTATION
1. NAME OF THE CANDIDATE
AND ADDRESS
Mr. PATEL NIRAVKUMAR ASHOKBHAI
DEPT. OF PHARMA CHEMISTRY
SET’s COLLEGE OF PHARMACY
S.R.NAGAR,
DHARWAD – 580002.
2. NAME OF THE INSTITUTION SET’s COLLEGE OF PHARMACY
S.R.NAGAR,
DHARWAD – 580002.
3. COURSE OF STUDY AND
SUBJECT
MASTER OF PHARMACY IN
PHARMACEUTICAL CHEMISTRY
4. DATE OF ADMISSION TO THE
COURSE
JUNE - 2010
2
5. TITLE OF THE TOPIC
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF QUINOLINE DERIVATIVES
6.0 Brief resume of the intended work
6.1 Need for study
The synthesis of heterocyclic derivatives has been an important part and is aimed in
modifying the action of drugs, particularly to reduce the side effects and to potentiate the
drug action. Today more than 60% drugs used in practice are synthesized derivatives and
day by day the scope of synthetic medicinal chemistry is increasing.
Quinoline is a heterocyclic scaffold. Several quinoline derivatives isolated from
natural resources or prepared synthetically are significant with respect to medicinal
chemistry and biomedical use. Indeed quinoline derivatives are some of the oldest
compounds which have been utilized for the treatment of a variety of diseases. Quinoline, a
distereoisomer of quinine was in the early 20th century acknowledged as the most potent of
the antiarrhythmic compounds isolated from the cinchona plant.1
The pyridine ring fused with the benzene nucleus in different ways with resultant
formation of quinoline, isoquinoline and quinolizinium salts. But quinoline has good
pharmacological attention. Quinoline ring structure is obtained by ortho condensation of
3
benzene ring with pyridine.2
Quinoline derivatives exhibiting variety of pharmacological properties like
antimalarial,3-5 antibacterial,6-9 antifungal,10-13 antitubercular,14-17 antileasimanial,18,19 anti-
HIV,20 antiviral,21 anti-convulsant,22,23 analgesic,24-26 anti-inflammatory, 24-26 anticancer 27,28
and antioxidant 29 activities.
Antimicrobial resistance has been an issue since the introduction into clinical use of the
first agents in the 1940s. Although the discovery and development of new classes of
antimicrobials through the 1960s presented an array of treatment options, these options for
some serious and life-threatening infectious diseases may now be more limited. 30
A numbers of recent clinical reports describe the increasing occurrence of methicillin-
resistant S. aureus and other antibiotic-resistant human pathogenic microorganisms in
world. Infections caused by those microorganisms pose a serious challenge to the medical
community and the need for an effective therapy has led to a search for novel antimicrobial
agents.
6.2 Review of literature
Anti-malarial activity: Charris JE et al.,3 have synthesized a series of 2-quinolinylmethylidene-5,7-dimethoxy
indanones which was prepared via base catalyzed Claisen-Schmidt condensation of 5,7-
dimethoxy-1-indanone with the appropriate 2-chloro-3-formylquinoline derivative.
Evaluation of their in vitro inhibition of β-hematin formation and hemoglobin
hydrolysis and in vivo efficacy in P. berghei suggest the antimalarial activity was
derived from inhibition of hemoglobinolytic proteases. Compounds 2-(2'-chloro-6'-
methoxy-3'-quinolinylmethylidene)-5,7- dimethoxy indanone.14
Comps R
9 H
10 6-CH3
12 8- CH3
14 6-OCH3
Meenakshi J et al.,4 have reported the synthesis of 2-substituted/2,5-disubstituted-8-
quinolinamines and some of their amino acid conjugates. Antimalarial evaluation was
4
carried out against drug-sensitive P. berghei strain and multi-drug resistant P. yoelii
nigeriensis strain and compound N 1-[4-(2-tert-butyl-6-methoxy-8-quinolylamino)-
pentyl]-(2S)-2,5-diaminopentamide & N1-[4-(2-tert-butyl-6-methoxy-8-
quinolylamino)pentyl]-(2S)-2-6-diaminohexanamide showed good antimalarial
activities.
Comps R
47 (CH2)3NH2
48 (CH2)4NH2
Peter BM et al.,5 have reported the synthesis of ring-substituted 4-aminoquinolines. The
entire compounds were further evaluated for their antimalarial activity and most of the
compound showed promising antimalarial activity against P. falciparum using a
fluorescent-active cell sorting (FACS) assay. It was found that all compounds were
more active against 3D7 and noted that the most active compounds had substituent’s
located at either the 6th or 7th position on the quinoline ring.
Antibacterial activity: Kidwai M et al.,6 have synthesized 7-(5'-Alkyl-1',3',4'-thiadiazol/oxadiazol-2'-yl-thio)-
6-fluoro-2,4-dimethylquinolines and 3-formyl-2-(2'-hydroxy-1',4'-naphthoquinon-3-yl)-
4-methyl/6-methyl/7-methyl/8-methylquinolines by the reaction of 5-alkyl-1,3,4-thia-
diazol/oxadiazol-2-thiols with 7-chloro-6-fluoro-2,4-dimethylquinoline. The
compounds were further screened for antibacterial activities. All compounds showed
promising antibacterial activity.
R X
C7H15 O
C11H23 S
5
Nandhakumar RN et al., 7 have reported Vilsmeier hack reaction on 4-
hydroxyquinolines lead to potential intermediate 4-chloro-3-formyl-2-(2-
hydroxyethene-1-yl)-quinolines. The intermediate was further utilized to prepare
quino[3,2-e][1,3]diazocines on treatment with phenylhydrazine hydrochloride. All the
synthesized diazepino quinoline derivatives were screened for their antibacterial and
antifungal as well as cytogenetic activities. Compounds showed good antibacterial and
antifungal activity against S. typhi and A. hydrophila respectively.
Comps R1 R2 R3 R4
8a H H H H
8b CH3 H H H
8c H CH3 H H
8d H H Cl H
8e CH3 H H CH3
Muhammad A et al.,8 have reported a series of quinoline-based chalcone by the
condensation of quinoline-3-carbaldehyde with acetophenone and N-substituted-3-
acetyl-4-hydroxy-2-quinoline with heterocyclic carbaldehyde. The prepared chalcones
were screen for antimicrobial activites against E. coli, P. aeruginosa, B. subtiles, K.
aerogens, S. albus, A. flavus, A. niger, R. rubera, L. lopofera and C. albicans. All the
prepared chalcones showed significant antimicrobial activities.
Kishor HC et al.,9 have synthesized some new substituted quinolinyl chalcones and
evaluated for antimicrobial activity against Gram positive and Gram negative strains
using a microdilution procedure. Synthesized compounds showed excellent activity
against S. aureus, B. subtillis, E. coli and S. typhosa microorganisms.
Antifungal activity: Carlos MG et al.,10 have diversed polyfunctionalized quinolines using Lewis acid-
catalyzed imino by Diels-Alder reactions between corresponding aldimines and tested
for antifungal properties. Among them, 4-pyridyl derivatives displayed the best
activities mainly against dermatophytes. The activity appears not be related neither to
6
the lipophilicity nor to the basicity of compounds.
Robert M et al.,11 have synthesized a variety of quinoline derivatives. All the prepared
derivatives were analyzed using the reversed-phase high performance liquid
chromatography (RP-HPLC) method for the lipophilicity measurement. The prepared
compounds were tested for their antifungal activity. 2-[(3-
hydroxyphenylimino)methyl]quinoline-8-ol(8),2-[(4-hydroxyphenylimino)
methyl]quinolin-8-ol (9) and 2-[(2,5-dichloro-4-nitrophenyl
amino)methoxy)methyl]quinolin-8-ol (10) showed antifungal activity comparable to or
higher than that of the standard fluconazole against strains Candida albicans ATCC
44859, Candida tropicalis 156 and Candida glabrata.
8 9 10
Rajendran SP et al.,12 have prepared some Schiff bases derived from 3-amino-2H-
pyrano[2,3-b]quinoline-2-one. 8-methyl-3-amino-2H-pyrano[2,3-b]quinoline-2-one
synthesized by reaction of 2-choro-3-formyl quinoline with ethyl glycinate
hydrochloride in pyridine at 120 ºC for 6 h. The compounds synthesized were screened
for their antifungal activities. Compound 3c, 3d and 3e showed good of antifungal
activity against Aspergillus niger.
Comps R1 R2 R3
3c H CH3 H
3d OCH3 H H
3e H OCH3 H
Gundibasappa KN et al.,13 synthesized N-[3-chloro-2-(2-chloroquinoline-3-yl)-4-
xoazetidin-1-yl]naphtho[2,1-b]furan-2-carboxamide derivatives. These synthesized
quioline derivatives were screened for antimicrobial activity. The compounds N-[2-(5-
methyl-2-chloroquinolin-3-yl)-3-chloro-4-oxoazetidin-1-yl] naphtho[2,1-b]furan-2-
7
carboxamide was found to be highly active as antibacterial agent against P. aerugenosa
and as antifungal agent against A. niger and C. albicans species.
Anti-tubercular activity: Alka M et al.,14 have studied the synthesis and characterization of some 4-amino
substituted 2,8-bis(trifluoromethyl)quinoline derivatives. All of the synthesized
compounds were primarily screened against Mycobacterium tuberculosis strain H37Rv
(ATCC 27294) at the single concentration of 6.25 μg/ml. The compound (2,8-bis-
trifluoromethylquinolin-4-yl)-(2-piperidin-1-yl-ethyl)amine showed good
antitubercular activity.
Marcus VN et al.,15 have synthesized series of 7-chloroquinoline derivatives and
evaluated for antibacterial activity against Mycobacterium tuberculosis H37Rv using
the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory
concentration (MIC) in µg/ml. Compounds N-(7-chloroquinolin-4-yl)octane-1,8-
diamine and N-(7-chloroquinolin-4-yl)decane-1,10-diamine exhibited a significant
activity at 6.25 and 3.12 µg/ml.
Ram Shankar U et al.,16 have carried out design, synthesis, molecular modelling and
characterization of 3-benzyl-6-bromo-2-methoxy-quinolines and amides of 2-[(6-
bromo-2-methoxy-quinolin-3-yl)-phenylmethyl]-malonic acid monomethyl ester. These
synthesized quinoline derivatives were screened for their antimycobacterial activity.
The compounds (±)6-bromo-3-(imidazol-1-yl-phenyl-methyl)-2-methoxy-quinoline(3),
6-bromo-2-methoxy-3-{phenyl-[4-(3-trifluoromethylphenyl)-piperazin-1-yl]-methyl}-
quinoline (8), (±)-6-bromo-2-methoxy-3-(phenyl-pyrazol-1-ylmethyl)-quinoline(17)
and (±)-6-{[(6-bromo -2-methoxy-quinolin-3-yl)-phenylmethyl]-amino}-chromen-2-
one(18) have shown 92–100% growth inhibition of mycobacterial activity with
minimum inhibitory concentration (MIC) of 6.25 µg/ml.
Comps R
3 Imidazolyl
8 1-(3-trifluoromethyl-phenyl)-piperazinyl
17 Pyrazolyl
18 6-amino-chromen-2-one
8
Sandra G et al.,17 have synthesized a series of 4-quinolylhydrazones and tested against
Mycobacterium tuberculosis at a concentration of 6.25 µg/ml. The synthesized
compounds bearing a methoxy group at C6 or C7 and 6, 7-methylendioxy substituent
quinoline derivatives showed a 100% inhibition of Mycobacterium tuberculosis growth
at a concentration of 6.25 µg/ml exhibited good anti-inflammatory activity.
Antileishmanial agent: Andre GT et al.,18 have synthesized novel quinoline derivatives and antileishmanial
efficacy determined in vitro against Leishmania chagasi, using extracellular and
intracellular parasite models. 2-methyl-3-[(2E)-3-phenylprop-2-enyl]quinolin-4-ol
demonstrated 8.3-fold greater activity than did the standard pentavalent antimony.
Nashira CV et al.,19 have reported the synthesis 2-n-propylquinoline (1), 2-
(2methoxyethenyl)quinoline (2) and 2-(2-hydroxyprop-2-enyl)quinoline (3) and
evaluated for antileishmanial activities.
Anti-HIV activity: Shuguang C et al.,20 have designed and synthesized thirty-two quinoline derivatives as
HIV-1 Tat–TAR interaction inhibitors. All the compounds showed high antiviral
activities by inhibiting the formation of SIV-induced syncytium in CEM174 cells.
Molecular modeling experiments indicated that these compounds may inhibit Tat–TAR
interaction by binding to Tat protein instead of TAR RNA.
Anti-Viral activity: Pramilla S et al.,21 have reported new series of quinoline derivarives prepared by
treating 2-methyl-4-chloroquinoline and 2-methyl-4-chloroacetyloxyquinoline with
sodium salts of 2-arylamino-5-mercapto-1,3,4-thiadiazoles to give 2-methyl-4-(2-
arylamino-1,3,4-thiadiazol-5-thio-yl)-quinoline and 2-methyl-4-(2-aryl-amino-1,3,4-
thiadiazol-5-thio-acetyloxy)-quinoline. The synthesized compounds evaluated for
antifungal activity against Helmintho sporum, antibacterial activity against Bacillus
subtilis and antiviral acivity against Tobacco mosaic virus.
Anticonvulsant activity: Xian-Yu Sun et al.,22 have synthesized a new series of 8-alkoxy-5,6-dihydro-
[1,2,4]triazino[4,3-a]quinolin-1-one derivatives. Their anticonvulsant activities were
evaluated by the Maximal Electro Shock (MES) test and their neurotoxicities were
evaluated by the rotarod neurotoxicity test. The results showed that 8-heptyloxy-5,6-
9
dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one 5t was the most potent with median
effective dose (ED50) value of 11.4 mg/kg, median toxicity dose (TD50) of 114.1 mg/kg.
The o-chloro derivative 5g exhibited the most potent activity and o-bromo derivative 5j
exhibited weaker activity than 5g. The derivatives 5h and 5i containing two chlorine
groups did not exhibited better anticonvulsant activity than derivatives with single
chlorine group.
Nichols AC et al.,23 have synthesized some new quinoline derivatives and screened for
anticonvulsant activity by Maximal Electro Shock, Pentylenetetrazole (PTZ) and
Threshold tonic extension (TTE) test.
Anti-Inflammatory: Sandhya B et al.,24 have reported the anti-inflammatory activity and antimicrobial
activity of some of 8-methyl-tetrazolo[1,5-a]quinoline derivatives.
Ashraf HA et al.,25 have synthesized novel 4-substituted-7-trifluoromethylquinoline
derivatives with nitric oxide releasing properties and tested for their in vivo anti-
inflammatory, analgesic and ulcerogenic properties, as well as their in vitro nitric oxide
release ability.
Abdel-Rahman BA et al.,26 synthesized a series of some novel pyrimido[4,5-b]quinolin-
4-ones derivatives and also evaluated their analgesic, anti-inflammatory and
antimicrobial activity. Among all active compounds 5and 8 possess high activity toward
Comps R
5g –C6H4(o-Cl)
5h –C6H3(2,4-Cl2)
5i –C6H3(2,6-Cl2)
5j –C6H4(o-Br)
5t n-C7H15
10
the fungi as compared with the reference drug nystatinan and found to have significant
peripheral analgesic activity.
Compound 5 Compound 8
Anticancer activity: Deady LW et al.,27 have reported a series of 11-oxo-11H-indeno[1,2-b]quinolines
bearing a carboxamide-linked cationic side chain at various positions on the
chromophore. This was studied to determine structure-activity relationships between
cytotoxicity and the position of the side chain.
Yeh-Long Chen et al.,28 have synthesized a certain linear 4-anilinofuro[2,3-b]quinoline
and angular 4-anilinofuro[3,2-c]quinoline derivatives and evaluated in vitro against the
full panel of NCI’s 60 cancer cell lines.
Anti-oxidant activity:- Lhassane I et al.,29 have reported new hexahydropyrimido[5,4-c]quinoline-2,5-diones
and 2-thioxohexahydropyrimido[5,4-c]quinoline-5-ones which were prepared in two
steps from ethyl 4-phenyl-6-methyl-2-oxo tetrahydropyrimidine-5-carboxylates or 4-
phenyl-6-methyl-2-thioxotetrahydropyrimidine-5-carboxylates. Their antioxidant
properties were evaluated by two methods: scavenging effect on 2, 2-diphenyl-1-
picrylhydrazyl (DPPH) radicals and scavenging effect on hydroxyl radicals.
Compounds containing thiourea moiety have better activity.
6.3 Objectives of the study1. To synthesize some newer derivatives of quinoline.
11
2. To monitor the progress of the reactions by TLC.
3. To purify the compounds by recrystallization and column chromatography methods.
4. To characterize the synthesized compounds by different analytical techniques such
as IR, NMR and Mass spectral data.
5. To evaluate the antimicrobial activities of newly synthesized quinoline derivatives.
7.0 Materials and methods:
7.1 Sources of data Chemical Abstracts
Indian Journal of Chemistry
Indian Journal of Heterocyclic Chemistry
Journal of Medicinal Chemistry
Journal of Heterocyclic Chemistry
European Journal of Medicinal Chemistry
Bioorganic and Medicinal Chemistry
Word wide web
J-Gate@ Helinet etc.
7.2 Method of collection of Data
A) Synthesis of the compounds: Chemicals and other reagents required for synthesis will be procured from standard
company sources. Compounds will be synthesized by using standard techniques. The
reactions will be monitored by TLC and purification of the compounds will be achieved by
standard procedures like recrystallization.
B) Characterization of the compounds: The synthesized compounds will be characterized by preliminary laboratory techniques
such as melting point, boiling point etc. Compounds synthesized will be confirmed by
FTIR, Mass Spectroscopy and NMR spectral data. The Mass and NMR spectral data of the
synthesized compound will be collected by sending the compounds to research centres at
IISc, Bangalore.
C) Invitro evaluation of antibacterial activity:
12
The MIC determination of the tested compounds will be carried out in side-by-
side comparison with ciprofloxacin and norfloxacin against Gram-positive (Staphylococcus
aureus, Bacillus subtilis) and Gram-negative bacteria (Klebsiella pneumoniae, Escherichia
coli) by broth microdilution method.31 Serial dilutions of the test compounds and reference
drugs will be prepared in Mueller-Hinton agar. Drugs (10 mg) will be dissolved in
dimethylsulfoxide (DMSO, 1 ml). Further progressive dilutions with melted Mueller-
Hinton agar will be performed to obtain the required concentrations of 1, 2, 4, 8, 16, 31.25,
62.5, 125, 250 and 500 mg/ml. The tubes will be inoculated with 105 cfu/ml (colony
forming unit/ml) and incubated at 37 0C for 18 h. The MIC will be the lowest concentration
of the tested compound that yields no visible growth on the plate. To ensure that the solvent
will have no effect on the bacterial growth, a control will be performed with the test
medium supplemented with DMSO at the same dilutions as used in the experiments.
D) Invitro evaluation of antitubercular activity:
The preliminary antitubercular screening for test compounds will be obtained
for M. tuberculosis H37Rv, the MIC of each drug will be determined by broth dilution
assay31 and is defined as the lowest concentration of drug, which inhibits 99% of bacterial
population present at the beginning of the assay. A frozen culture in Middlebrook 7H9
broth will be supplemented with 10% albumine dextrose catalase and 0.2% glycerol will be
thawed and will be diluted in broth to 105 cfu/ml for M. tuberculosis and will be used as the
inoculum. In the assay U-tubes will be used to accommodate compounds in 1-500 mg/ml
dilutions. Each test compound will be dissolved in DMSO and then diluted in broth twice at
the desired concentration. The final concentration of DMSO in the assay medium will be
1.3%. Each U-tube will be then inoculated with 0.05 ml of standardized culture and then
will be incubated at 37 0C for 21 days. The growth in the U-tubes will be compared with
visibility against positive control (without drug), negative control (without drug and
inoculum) and with standard isoniazid.
7.3 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
NO
13
7.4 Has ethical clearance been obtained from your institution in case of
7.3?NA
8.0 REFERENCES:
1. Sudharshan M, Zehra T, Sanjay B. Advances in the syntheses of quinoline and
quinoline annulated ring systems. Current Org Chem 2008;12:1116-83.
2. Raj KB. Heterocyclic chemistry. 4th ed. New delhi(India): New age
international;2005. p. 366.
3. Charris JE, Lobo GM, Camacho J, Ferrer R, Barazarte A, Domínguez JN et al.
Synthesis and antimalarial activity of (E) 2-(2'-chloro-3'-quinolinylmethylidene)-
5,7-dimethoxyindanones. Letters Drug Design Discovery 2007;4: 49-54.
4. Meenakshi J, Suryanarayana V, Sandeep S, Rahul J. Synthesis and blood-
schizontocidal antimalarial activities of 2-substituted/2,5-disubstituted-8-
quinolinamines and some of their amino acid conjugates. Bioorg Med Chem
2004;12:1003-10.
5. Peter BM, John S, Ally PL, Jennifer LW, Joseph LD, Kiplin GR. Synthesis of
ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities.
Bioorg Med Chem Lett 2005;15:1015-8.
6. Kidwai M, Bhushan KR, Sapra P, Saxena RK, Gupta R. Alumina supported
synthesis of antibacterial quinolines using microwaves. Bioorg Med Chem
2000;8:69-72.
7. Nandhakumar R, Thangaraj S Palathurai SM. Isolation of 4-chloro-3-formyl-2-(2-
hydroxyethene-1-yl) quinolines by Vilsmeier haack reaction on
quinaldines:construction of diazepino quinoline heterocyclesand their
antimicrobial and cytogenetic studies. Acta Pharm. 2003(53):1-14.
8. Muhammad A, Munawar AM, Hamid LS. Antimicrobial activity and synthesis of
quinoline based chalcones. J Allplied Sci 2007;7(17):2485-9.
9. Kishor HC, Mayank JP, Dhaval BV. Design, synthesis and evaluation of novel
quinolyl chalcones as antibacterial agents. ARKIVOC 2008;(xii):189-97.
10. Carlos MG, Vladimir VK, Maximiliano AS, Sandra LÁ, Susana AZ. In vitro
antifungal activity of polyfunctionalized 2-(hetero)arylquinolines prepared through
14
imino diels–alder reactions. Bioorg Med Chem 2008;16:7908-20.
11. Robert M, Josef J, Vladimir B, Luis S, Halina N, Barbara P et al. Antifungal
properties of new series of quinoline derivatives. Bioorg Med Chem
2006;14:3592-8.
12. Rajendran SP, Karvembu. Synthesis and antifungal activities of Schiff bases
derived from 3-amino-2H-pyrano[2,3-b]quinoline-2-ones. Indian J Chem sec B
2002;41:222-4.
13. Gundibasappa KN, Gowdara KP, Marlingaplara NK, Vijayavittala PV, Kittappa
MM. Synthesis of novel nitrogen containing naphtho[2,1-b]furan derivatives and
investigation of their antimicrobial activities. Archive Org Chem 2006(xv):160-8.
14. Alka M, Villendra SN, Uma R. Synthesis and antimycobacterial activities of
certain trifluoromethyl-aminoquinoline derivatives. . Archive Org Chem
2006(x):220-7.
15. Marcus VN, Karla CP, Carlos RK, Mônica AP, Marcelle LF, Maria CSL.
Synthesis and in vitro antitubercular activity of a series of quinoline derivatives.
Bioorg Med Chem 2009;17:1474-80.
16. Ram SU, Jaya KV, Nageswara RV, Vivek S, Shailesh SD, Jyoti C. Design,
synthesis, biological evaluation and molecular modelling studies of novel
quinoline derivatives against Mycobacterium tuberculosis. Bioorg Med Chem
2009;17:2833-41.
17. Sandra G, Luisa S, Maria A, Pierangela T, Luisa C, Salvatore SC et al.
Development of antitubercular compounds based on a 4-quinolylhydrazone
scaffold. Further structure activity relationship studies. Bioorg Med Chem
2009;17:6063-72.
18. Andre GT, Ana Claudia MP, Carlos AB, Fernanda SM, Samanta ETB, Maria
Amelia BS et al. Synthesis and antileishmanial activities of novel 3-substituted
quinolines. Antimicrob Agents Chemother. 2005;49(3):1076-80.
19. Nashira CV, Christine H, Joel V, Alain F, Christian B, Bruno F et al. Selection of
the most promising 2-substituted quinoline as antileishmanial candidate for clinical
trials. Biomed Pharmacother 2008;62:684-9.
20. Shuguang C, Ran C, Meizi H, Ruifang P, Zhiwu T, Ming Y. Design, synthesis and
biological evaluation of novel quinoline derivatives as HIV-1 Tat–TAR interaction
inhibitors. Bioorg Med Chem 2009;17:1948-56.
21. Pramilla S, Garg SP, Nautiyal SR. Some new biologically active quinoline
15
analogues. Indian J Heterocycl Chem 1998;7:201-4.
22. Xian-Yu S, Lei Z, Cheng-Xi Wa, Hu-Ri P a, Zhe-Shan Q. Design, synthesis of 8-
alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-ones with anticonvulsant
activity. Eur J Med Chem 2009;44:1265-70.
23. Nicolas AC, Lemone LY. Quinoline acid derivatives. United States Patent. 1998
Jul 21;5783700.
24. Sandhya B, Suresh K. Synthesis of Schiff’s bases of 8-methyl-tetrazolo[1,5-
a]quinoline as apotential anti-inflammatory and antimicrobial agents. Indian J
Chem sec B 2009;48:142-5.
25. Ashraf HA, Hegazy GH, El-Zaher AA. Synthesis of novel 4-substituted-7-
trifluoromethylquinoline derivatives with nitric oxide releasing properties and their
evaluation as analgesic and anti-inflammatory agents. Bioorg Med Chem
2005;13:5759-65.
26. Abdel-Rahman BA, El-Enanyb MM, Mahmoud MN. Synthesis, analgesic, anti-
inflammatory and antimicrobial activity of some novel pyrimido[4,5-b]quinolin-4-
ones. Bioorg Med Chem 2008;16:3261-73.
27. Deady LW, Desneves J, Kaye AJ, Finly GJ, Baguley BC, Denny WA. Positioning
of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinoline carboxamide
anticancer agent effect on cytotoxicity. Bioorg Med Chem 2001;9:445-52.
28. Yeh-Long C, Chen IL, Tai-Chi W, Chein-Hwa H, Cherng-Chyi T. Synthesis and
anticancer evaluation of certain 4-anilinofuro[2,3-b]quinoline and 4-
anilinofuro[3,2-c]quinoline derivatives. Eur J Med Chem 2005;40:928-34.
29. Lhassane I, Arulraj N, Laurence N, Catherine G, Alain X, Robert JF. Synthesis
and antioxidant activity evaluation of new hexahydropyrimido[5,4-c]quinoline-
2,5-diones and 2-thioxohexahydropyrimido[5,4-c]quinoline-5-ones obtained by
biginelli reaction in two steps. Eur J Med Chem 2008;43:1270-5.
30. Kumar RN, Suresh T, Dhanabal T, Mohan PS. A novel approach to 12-chloro-3-
thio-4H-quinoline[3,2-e][ 1,3]diazocines via Vilsmeier hack reaction. Indian J
Chem sec B 2007;46:995-1000.
31. Talath S, Gadad AK. Synthesis, antibacterial and antitubercular activities of some
7-[4-(5-amino-[1,3,4]thiadiazole-2-sulfonyl)-piperazin-1-yl]fluoroquinolonic
derivatives. Eur J Med Chem 2006;41:918-24.
16
9. SIGNATURE OF THE
STUDENT
10. REMARK OF THE GUIDE
The above mentioned information and literature has been extensively investigated, verified
and was found to be correct. The present study will be carried out under my supervision
and guidance.
11. 11.1 NAME AND DESIGNATION
OF THE GUIDE
11.2 SIGNATURE
Dr. S. D. JOSHI M. Pharm, Ph.D.PROFESSOR & HEAD,DEPT. OF PHARMACEUTICAL CHEMISTRY,SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD – 580002.
11.3 NAME AND DESIGNATION
OF CO-GUIDE
11.4 SIGNATURE
------------------------
11.5 HEAD OF THE
DEPARTMENT
11.6 SIGNATURE
Dr. S. D. JOSHI M. Pharm, Ph.D.PROFESSOR & HEAD,DEPT. OF PHARMACEUTICAL CHEMISTRY,SET’s COLLEGE OF PHARMACY, S.R.NAGAR, DHARWAD – 580002.
12. 12.1 REMARK OF THE
PRINCIPAL
12.2 SIGNATURE
The above mentioned information is correct and I
recommend the same for approval.
Dr. V. H. KULKARNI M. Pharm, Ph.D.PROFESSOR & PRINCIPAL, SET’s COLLEGE OF PHARMACY,S.R.NAGAR, DHARWAD – 580002.
17