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) / Suresh Kumar
S/o. Harnam Singh
Village-Tikkeri Ghuralan
P.O-Ludder Mahadev
Teh.- Bhoranj
Distt.- Hamirpur
(H.P) 176045
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 / 14/05/2007
5 / Title of the topic / “SYNTHESIS, CHARACTERIZATION , ANTIMICROBIAL AND ANTI-DIABETIC ACTIVITY OF FEW THIOSEMICARBAZIDES DERIVED FROM ACETYL COUMARIN”
6 / BRIEF RESUME OF THE INTENDED WORK
6.1 Need ForThe Study :
Coumarins not only occur in nature but also posses very good physiological activities. It had been known since 1921. Link and coworker found that cattle feeding on spoiled sweet hay suffered from a condition characterized by sharp in crease of blood clotting time. The pathogenic hemorrhagic principle of sweet clover hay was found by them to be 3, 31-methylenebis– (4-hydroxy coumarin) popularly called Dicoumarol. It was synthesized by reacting4-hydroxy coumarin with formaldehyde and found to be a good anticoagulant of blood. Since this discovery and also because of its high reactivity, the chemistry of 4-hydroxy coumarin has assumed great importance1-2.
The compounds containing thione (>C=S) and thiol (>C-SH) groups occupy an important position among organic reagents as they posses many applications in industry, in medicine and analytical chemistry.
Thiosemicarbazides and thiosemicabazones possess good cheating properties and diversified biological activities against virus,protozoa, small pox, certain kinds of Tumors and bacteria. Considering all the above facts. It was thought that if sulfonamides group could be introduced to thiosemicarbazones moiety, the resulting compound might have some significant biological properties3.
Various hydrazines derivatives and semi-carbazides have been known to inhibit monoamine oxidase activity. Monoamine oxidase inhibitors had also been reported to exhibit marked Anti-convulsant activity4.
Various methods for synthesis of coumarins and thiocoumarines, coumarinoacetyl pyrazoles have shown moderative good activities against all fungi and bacteria5-9 .
Chromen-2-one derivatives posses diverse Biological properties such as Anti bacterial , Anti-fungal , Anti-neoplastic , Anti-tubercular , Anthalmentic , Neuroleptic , Anti-HIV , recently chromen-2-ones were reported to posses selective dopamine D4 antagonist activities10.
Some new Thiozolidines and Azolidinones of 6-amino Coumarins , 7,8-dihydroxy-4-methyl coumarins , 4-hydroxy coumarin posses Anti-bacterial , physiological , Anti-cougalant , Spasmolytic , Bacteriostatic ,Anti-toumer activity11-13.
Hence there is a need for Synthesis of compounds containing Coumarin ring and Thione group in hope of getting compound with better Biological and Pharmacological Activities.
As a part of our studies concerning, the Synthesis of Coumarin based fused heterocyclic compounds, we are interested in preparationof coumarin based fused substituted thio-semicarbazide derivatives.
6.2 Review of literature:
An extensive survcy of literature to be done by referring chemical abstracts, various international research journals in our college libraries, libraries of kuvempu university shimoga, Karnataka university Dharwad, Mysore University 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.S.C Bangalore.
6.3 Objectives of study:
The main objective of the present work is to synthesize the compounds containing coumarin ring and thione group in hope of getting potent biological and pharmacological compounds.In present work for the synthesis of titled compounds; acetyl coumarin
will be treated with various substituted thiosemicarbazides. The structures of the compounds will be conformed by spectroscopic data and will be screened for various biological and pharmacological activities.
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 confirmation (I.R.,NMR and Mass spectra etc.)
c)Biological and pharmacological screening and the results of activities.
7.1 Source of data:
Various national and international journals.
Chemical Abstracts.
Standard text books for carrying out screening of pharmacological activities.
Indian pharmacopoeia.
7.2 Methods of collect of data:
(Including sampling procedure if any)
a)Synthetic methodology :
Synthetic strategy for target molecules involves following procedure:
The reaction of salicylaldehyde with ethylacetoacetate in presence of piperidine give yellow solid mass of Acetyl-Coumarin14-15 which was fused with substituted thiosemicarbazide in ethanol medium to afford the corresponding Acetyl coumarin thio semicarbazide derivatives.
Reaction will be monitored by T.L.C. and products purified by recrystallisation.
b)Spectroscopic data:
IR of all new compounds will be obtained by using spectrophotometers available in our college, NMR and mass spectroscopic data will obtained from I.I.Sc. Bangalore and I.I.T. Madras etc.
c)Pharmacological and Biological Screening:
Antimicrobial activity16-17: All the synthesized compounds will be evaluated for Anti-microbial activity by cup plate method.
Anti-diabetic activity18-21: Selected compounds will be subjected to screen for Anti-diabetic activity will be carried out by alloxan induced diabetic rat.
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 Anti-microbial activity and Anti-diabetic activity requires albino rats (Wistar strain, either sex 150-200g), Analgesic activity requires mice (Swiss strain either sex 20-25g) which will be sacrificed.
7.4Has ethical clearance been obtained from your institution in case of 7.3.
Ethical clearance is available, Reg.No.157/1999CPCSEA.
8 / LIST OF REFERENCES :
1)K.N.Trivedi.,S.S.Madhava Rao.,S.V.Misntry.,et al.2001 “Chemistry of 4-hydroxycoumarin”.J.Indian Chem. Soc., 78: 579-595.
2)Surendra Nath Pandeya., “A text book of medicinal chemistry”. SG Publisher,2000. 441 pp.
3)Sandhya Gandheand Mangla Dave Goutam., 2003 “Synthesis and Antibacterial Activity Screening of 1-(2-Methyl-4-N-Cyanoethyl-N-Benzenesulphonyl Aminobenzylidene) 4-Aryl Thiosemicarbazone”.Asian Journal of Chemistry., 15: 781-784.
4)M.I.Husain and Mohd. Amir., 1986 “Synthesis of some New Substituted Thiosemicarbazides and Triazoles as Possible Anticonvulsants”. J.Indian Chem. Soc.,LXIII: 317-319.
5)M.S.Gaikawad.,et al. 2000 “Synthesis of Newer Coumarinoacetyl Pyrazoles and Their Antimicrobial Activities”.Indian Journal of Heterocyclic Chemistry.,9: 315-316.
6)M.Natarajan and V.T.Ramakrishanan., 1984 “A New Route for the Coumarins, Thiacoumarins and Carbostyrils”.Indian Journal of Chemistry., 23B: 720-727.
7)V.V.Mulwad and M.B.Dalvi., 2000 “Synthesis of N-6-coumarinyl Maleimide and its Diels-Alder Reaction With Anthracene”. Indian Journal of Heterocyclic Chemistry., 9: 165-168.
8)Pratibha Sharma and Shreeya Pritmani., 1999 “Synthesis, characterization and antimicrobial studies of some novel 3-arylazo-7-hydroxy-4-methylcoumarins”. Indian Journal of Chemistry., 38B: 1139-1142.
9)M.E.Abd El-Fattah., 1998 “Synthesis and Antimicrobial Activity of Heterocyclic Compounds Containing Coumarin Moiety”. Indian Journal of Heterocyclic Chemistry., 8: 111-116.
10)S.H.Bhosale., et al.2006 “Synthesis and Antipsychotic Activity of New coumarinoacetamides”. Indian Journal of Heterocyclic Chemistry.,15: 267-270.
11)V.V.Mulwad and Jyoti M.Shirodkar.,2002 “Synthesis and Biological Activity of Some New Thiazolidinones and Azetidinones of 6-Amino Coumarin”. Indian Journal of Heterocyclic Chemistry.,11: 291-294.
12)Shallu Sachdeva .,et al. 2006 “Chemical speciation and computer modeling studies on interaction of an antioxidant 7,8-dihydroxy-4-methylcoumarin with bivalent metal ions”. J.Indian Chem. Soc., 83: 356-360.
13)V.V.Mulwad and Jyoti M.Shirodkar.,2002 “Synthesis and Biological Activity of some New Schiff`s Bases, Thiazolidinones and Azetidinones of 4-Hydroxy Coumarin”. Indian Journal of Heterocyclic Chemistry.,11: 199-202.
14) A.I.Vogel.“A Text Book of Practical Organic Chemistry”ELBS, 4THEdition, 802pp.
15)Vijayananda Krishna Revankar., Ph.D. Thesis on “Chemistry of some Coordination Compounds” submitted to Karnatka university Dharwad.1988. 114-115 pp.
16)L.M.Patel, K.H.Chikhalia and P.S.Desai.,2005 “Synthesis of substituted s-triazine derivatives and studies of their antimicrobial activities”. J.Indian Chem. Soc.,82: 83-85.
17)M.Yildiz, B.Dulger , S.Y.Koyuncu and B.M.Yapier.,2004 “Synthesis and antimicrobial activity of bis(imido) Schiff bases derived from thiosemicarbazide with some 2-hydroxyaldehydes and metal complexes”. J.Indian Chem. Soc.,81: 7-12.
18)S.Badole., et al. 2006 “Antihyperglycemic activity of aqueous extract of leaves of Cocculus hirsutus (L.) Diels in alloxan-induced diabetic mice”.Indian J. Pharmacol38: 49-53.
19)D.Ray., et al. 2006 “Antipyretic, antidiarrhoeal, hypoglycaemic and hepatoprotective activities of ethyl acetate extract of Acacia catechu Wild. In albino rats”. Indian J. Pharmacol 38: 408-413.
20)Glauce SB Viana., et al.2004 “Hypoglycemic and anti-lipemic effects of the aqueous extract from Cissus sicyoides”.BMC Pharmacology 4: 1-7.
21)Nafisa PC Fernandes., et al. 2007 “An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract”. BMC Complementary and Alternative Medicine7: 29:1-8.
Signature of Candidate / (MR.SURESH KUMAR)
10 / 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.
11 / Name and Designation
(in block letters)
11.1 GUIDE
Guide ship reference no. of RGUHS
ACA/CDC/PGT-M.Ph/SCS/02/2005-06
Date: 27-09-2005.
11.2 Signature.
11.3 Co-guide(if any)
Guide ship reference no. of RGUHS
ACA/ PGT-M.Ph/SCS/02/99-2000/5821
Date: 05-06-1999..
11.4 Signature
11.5 Head Of The Department
Guide ship reference no. of RGUHS
ACA-2/RP-TEA/01/97-98
Date:.03-06-1998.
11.6 signature / Dr.B.H.M. JAYAKUMAR SWAMY Professor,
P.G. Dept. of Pharmaceutical Chemistry,
S.C.SCollege of Pharmacy,
Harapanahalli-583131.
Davanegere-Distt.
Dr.B. SHIVAKUMAR
Professor,
P.G. Dept. of Pharmaceutical Chemistry,
S.C.SCollege of Pharmacy,
Harapanahalli-583131.
Davanagere-Distt.
Dr. E. JAYACHANDRAN
Professor and Head.
P.G. Dept. of Pharmaceutical Chemistry,
S.C.SCollege of Pharmacy,
Harapanahalli-583131.
Davanagere-Distt.
12 / 12.1 Remarks of the principal
12.2 signature / (DR. S. RAMACHANDRA.SETTY)