RajivGandhiUniversity of Health Sciences, Karnataka
Bangalore
ANNEXURE-II
PROFORM FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of the Candidate and Address(In Block letters) / P.N.BALAJI
S/o. P.Nagaraja.setty
D.No.142, 10th ward, Main road
Gowler pet,
Harapanahalli-583131
Davanegere-Dist, Karnataka.
2 / Name of the Institution / T.M.A.E.Society’s
S.C.S.College of Pharmacy
Harapanahalli-583131
3 / Course of Study and Subject / M.Pharm ( previous )
Pharmaceutical chemistry
4 / Date of Admission to course / 09/06/ 2007
5 / Title of the Topic / “SYNTHESIS,CHARACTERISATION, ANTI-MICROBIA AND WOUND HEALING ACTIVITY OF SOME NEW THIOSEMICARBAZIDE DERIVATIVES STARTING FROM HALOGENATED QUINOLINE”
6 / BRIEF RESUME OF INTENDED WORK.
6.1Need for the study:
The structure of Quinoline was known since 1908 and provided total synthesis by Woodward and Dogering in 1945. It was the structural model for all of the other quinoline anti malerials1-4.
Quinolines and benzo/hetero-fused analogues have attracted great attention of medicinal and synthetic chemists because of their presence in natural products and physiological activities.
The fused Quinolines are known to bind DNA with high affinity, inhibit DNA topoisomerase and display cytotoxic and antitumer activity5-9.
The compounds containing thione ( >C=S ) and thiol ( >C-SH ) groups occupy an important position among organic reagents as they possess many applications in industry, in medicine and analytical chemistry.
Quinoline based fused heterocyclic compounds have been reported various biological activities such as Anti-mycobacterial10-11, Anti-convulsant12, Anti-inflammatory13, Anti-viral14-15and Anti-microbial16-17 activities.
Hence there is a need for synthesis of compounds containing quinoline ring and thione group in hope of getting compounds with better biological and pharmacological activity.
As a part our studies concerning, the synthesis of quinoline based fused heterocyclic compounds, we are interested in preparation of quinoline based fused substituted Thiosemicarbazide derivatives.
6.2Review of Literature :
An extensive survey of literature to be done by referring chemical abstracts, various international research journals in our college library, libraries of Kuvempu university Shimoga, Karnataka University Dharwad, Mysore and Bangalore University Bangalore, Gulbarga University Gulbarga. The literature survey will also be made by visiting the various websites through internet and also by availing CD ROM facilities I.I.Sc.Bangalore.
6.3Objectives of Study :
The main objective of the present work is to synthesize the compounds containing quinoline ring and thione group in hope of getting potent Biological and Pharmacological compounds. In present work for the synthesis of titled compounds; Haloginated-3-Formyl Quinolines will be treated with various substituted Thiosemicarbazide. The structure of the compound will be conformed by spectroscopic data and will be screened for anti-microbial and wound healing activity.
7 / MATERIALS AND METHODS :
The necessary data will be generated by laboratory experimentation technique this includes,
a)Synthesis of Target molecules.
b)Spectroscopic data of new compounds for structural confirmations (I.R, NMR and Mass spectra etc.)
c)Biological and Pharmacological screening and the results of activities.
7.1Source of Data :
- Various national and international journals.
- Chemical Abstracts.
- Standard text book for carrying out screening of Pharmacological activities.
- Indian pharmacopoeia.
( Including sampling procedure if any )
a)Synthetic methodology :
The Synthetic strategy for target molecules involves following procedure:
The reaction of acetanilide with Vilsmeier-Haack reagent gave halogenated 3-formyl quinoline18, which was fused with substituted Thiosemicarbazide in ethanol medium to afforded the corresponding halogenated 3-formyl quinoline Thiosemicarbazide derivatives.
Reaction will be monitored by T.L.C. and products purified by recrystallisation.
b)Spectro Scopic Data :
I.R. of all new compounds will be obtained by using spectrophotometers available in our college, NMR and Mass spectroscopic data will obtain from I.I.Sc.Bangalore and I.I.T. Madras etc.
c)Pharmacological and Biological Screening:
Anti-microbial activity16-17: All the Synthesized compounds will be evaluated for Anti-microbial activity by Cup Plate method.
Wound Healing activity19-20: Selected Synthesized compounds will be subjected to screen for Wound healing activity by using excision wound model.
7.3 Does the study require any investigation (or) interventions to be conducted on patients (or) other humans (or) animals? If so please describe briefly :
Investigation of Wound healing activity requires albino rats (Wistar strain, either sex 150-200 g).This will not be Sacrificed.
7.4 Has Ethical Clearance been obtained from your institution in case of 7.3.
Ethical clearance is available, Reg. No. 157/1999 CPCSEA.
8 / List of References :
1.Timothy J.Egan., et al. 2000 “Structure-function relationships in aminoquinolines: Effect of amino and chloro groups on Quinoline-hematin complex formation, inhibition of β-Hemantin formation, and anti-plasmodial activity”. J.Med.Chem, 43:283-291.
2.Sung-eun Lee. et al.2002 “Synthesis and evaluation of new anti-malarial analogues of Quinoline alkaloids derived from cinchona ledgerian moens ex trimen” Bioorg. Med.Cham.Lett, 12:1351-1355.
3.Vlahov R., Vlahov J., St.Parushev.1990 “Synthesis of some new Quinoline derivatives potential anti-malarial drugs”.Pure& Appl.Chem. 62:1303-1306.
4.Block John H.and John M Beale Jr.Wilson and Giswald’s. The text book of organic medicinal and pharmaceutical chemistry, Philadelphia: Lippincott Williams and Wilkins- A wolters kluwer, 2004, 282pp.
5.Myung-Eun Suh., SO-Young park and Chong-Ock Lee.2001 “Synthesis of Pyridino [2, 3-f] indole-4, 9-dione 6, 7-disubstituted Quinoline-5, 8-dione derivatives andevaluation on their cytotoxic activity”. Bioorg.Med.Chem, 9:2979-2986.
6.Thierry Besson., et al.2000 “Expeditious Synthesis and cytotoxic activity of new cyanoindolo [3, 2-c] quinolines and benzimidazo [1, 2-c] quinozolines”.Bioorg.Med.Chem.Lett, 10:2183-2185.
7.Jean-pierre Henichart., et al.2004 “DNA binding to guide the development of tetrahydroindeno[1,2-b]pyriodo[4,3,4-de]quinoline derivatives as cytotoxic agents” J.Med.Chem.,47:3665-3673.
8.Cherng-Chyi Tzeng., et al.2005 “Synthesis and cytotoxic evaluation of certain 4-anilino-2-phenylquinoline derivatives”.European Journal of Medicinal Chemistry. 40:792-797.
9.Palumbo M., et al.2000 “Pyrrolo-quinoline derivatives as potential antineoplastic drugs”Bioorg.Med.Chem,8:1415-1422.
10.Rahul Jain., et al.2004“Ring Substituted quinolines. Part 2: Synthesis and anti-mycobacterial activities of ring-substituted quinolinecarbohydrazide and ring-substituted quinolinecarboxamide analogues”.Bioorg.Med.Chem,12:6465-6472.
11.Padmakar V.Khadikar., et al.1999 “Quantitative structure-activity relationship studies on antituberculotic N1-cyclopropylquinolones using Szeged Index (Sz)”Indian J.Chem, 38A:1203-1208.
12.Zhe-ShanQuan., et al.2005 “Synthesis and anticonvulsant activity of 7-alkoxyl-4, 5-dihydro-[1, 2, 4] triazolo [4,3-a]quinolines”. Bioorg.Med.Chem.Lett, 15:4803-4805.
13.Yeh-Long Chen., et al.2003 “Synthesis and anti-inflammatory evaluation of 9-phenoxyacridine and 4-phenoxyfuro [2,3-b]quinoline derivatives. Part 2” Bioorg.Med.Chem. 11:3921-3927.
14.Jeand’Angelo., et al.2004 “Linker-modified quinoline derivatives targeting HIV-1 integrase: synthesis and biological activity”. Bioorg.Med.Chem.Lett, 14:2473-2476.
15.Didier Desmaele., et al.2005 “HIV-1 replication inhibitors of the styrylquinoline class: introduction of an additional carboxyl group at the C-5 position of the quinoline”Tetrahedron letters, 46:2201-2205.
16. Adnan A.Bekhit., et al.2004 “Tetrazolo [1,5-a]quinoline as a potential promising new scaffold for the synthesis of novel anti-inflammatory and anti-bacterial agents”.European journal of Medicinal Chemistry, 39:249-255.
17. Jaroslaw Polanski., et al.2006 “Anti-fungal properties of new series of quinoline derivatives”. Bioorg.Med.Chem. 14:3592-3598.
18.Otto Meth-Cohn., Bramha narine, and Brian Tarnowski.1981 “A versatile new synthesis of quinolines and related fused pyridines part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes”. J.C.S.Perkin, 30:1520-1530.
19. R.M.Perez Gutierrez, R.Vargas. S. 2006 “Evaluation of the wound healing proreties of Acalypha langiana in diabetic rat’s”.Fitoterapia, 77:286-289.
20. Manish Nivaskar, Aryamitra Banergy et al.2006, “Wound Healing Activity of Hemolok (Sepgard) Gel in Sprague Dawley Rats” Adv.Pharmacol.Toxicol. 7 (1):21-23.
Signature of Candidate. / ( P.N.BALAJI )
Remarks of the Guide. / The Mentioned Title Compound will be Synthesized and Screened for the activity. They are confirmed by the Spectroscopical Studies under the guidance of me in the P.G.Department of Pharmaceutical Chemistry of our College.
Name and Designation.
( in block letters )
11.1 GUIDE:
Guide ship Reference No. of RGUHS
ACA/CDC/PGT-M.Ph/SCS/O2/2005-06
Date: 27-09-2005.
11.2 Signature.
11.3Co-guide (if any )
Guide ship Reference No. of RGUHS
ACA/PGT-M.Ph/SCS/02/99-2000/5821
Date: 05-06-1999.
11.4Signature.
11.5Head of the Department
Guide ship Reference No. of RGUHS
ACA-2/RP-TEA/01/97-98/3-6-98
11.6 Signature. / Dr. B.H.M.JAYKUMAR SWAMY
Professor,
P.G.Dept.of Pharmaceutical Chemistry,
S.C.S.College of Pharmacy,
Harapanahalli-583131.
Davanegere-Dist.
Dr. B.SHIVAKUMAR
Professor,
P.G.Dept.of Pharmaceutical Chemistry,
S.C.S.College of Pharmacy,
Harapanahalli-583131.
Davanegere-Dist.
Dr. E. JAYACHANDRAN
Professor and Head,
P.G.Dept.of Pharmaceutical Chemistry,
S.C.S.College of Pharmacy,
Harapanahalli-583131.
Davanegere-Dist.
12.1 Remarks of the Principal
12.2Signature. / Dr.S.RAMACHANDRA.SETTY