Download Synthesis characterization and pharmacological

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA,
BANGALORE
ANNEXURE-II
PROFORM FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
NITIN PATEL
S/o Bhanuprasad Patel
At : T.Palla, Post : Madhavas,
(389230)Ta: Lunawada,
Dist : Panchamahal, Gujarat.
T.M.A.E. Society’s
S.C.S College of Pharmacy
Harapanhalli-583131
M.Pharm ( Previous )
Pharmaceutical chemistry.
5TH July,2008
1
Name of the candidate and address
(In block letters)
2
Name of the institution
3
Course of Study and Subject
4
5
Date of admission to course
Title of the topic
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BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR STUDY
Link and coworker found that cattle feeding on spoiled sweet hay suffered from a condition
characterized by sharp increase of blood clotting time. The pathogenic hemorrhageic principle of
sweet clover hay was found by them to be 3, 31 - methylenebis – (4-hydroxy Coumarin) popularly
called Dicoumarol. It was synthesized by reacting 4-hydroxy Coumarin with formaldehyde and
found to be a good anticoagulant of blood.
“SYNTHESIS, CHARACTERIZATION, IN-VITRO ANTIOXIDANT AND ANTI-MICROBIAL
ACTIVITIES OF NOVEL COUMARIN
THIOSEMICARBAZONES”
Coumarin is widely available in plant kingdom as the active constituent in various plants.
Many of natural occurring coumarins posses wide range of biological and pharmacological
activities.
Literature on biological and pharmacological activities of synthetic coumarins is
innumerous1-4. Coumarins are known to posess anti-inflammatory, antioxidant5, HIV reverse
transcriptase inhibitory activity6, antiviral7, anti-tumor activity8, cytotoxic agents9,antitubercular10
agents.
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. Variety of thiosemicarbazones are synthesized and evaluated for their useful
biological and pharmacological activities like antiviral11-13, antibacterial and antitubercular
activity14, antiamoebic acitivity15, anticancer and cytotoxic activities16-17.
However there are few reports on biological significance of coumarin thiosemicarbazones.
Hence the present work is designed to synthesize novel thiosemicarbazones of coumarins and to
evaluate their biological activities like antimicrobial and antioxidant activity.
6.2 Review 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 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 novel compounds containing coumarin
ring and thione group in hope of getting potent biological agents. Biological acivities of
synthesized compounds like antibacterial and antioxidant activities will evaluated. Antibacterial
activity of compounds will be evaluated against gram positive and gram negative pathogens by
MIC method18. Antioxidant potential of the compounds will be carried out by in-vitro models
against various types of free radicals19-20.
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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.,H1 NMR and Mass
spectra etc).
c) Anti-microbial and In vitro Anti-Oxidant screening and result of activities.
7.1 Source of data:
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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 followings procedure.
The reaction of salicylaldehyde with Ethylacetoacetate in presence of piperidine give
yellow solid mass of Acetyl-Coumarin21-23, which was fused with substituted
thiosemicarbazide in ethanol medium in presence of glacial acetic acid to afford the
corresponding Acetyl Coumarin thiosemicabazone derivatives.
Reaction will be monitored by TLC and product purified by recrystllisation.
b) Spectroscopic data:
IR 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) In vitro Anti-Oxidant and Biological screening:
Anti-Microbial activity 18: All the synthesized compounds will be evaluated for
Anti-microbial activity by MIC method.
In-Vitro Anti-Oxidant activity 19-20: Selected compounds will be subjected to screening
for In-vitro Anti-Oxidant activity.
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:
NO
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LIST OF REFERENCES :
1) Borges F, Roleira F, et al. “Simple coumarin and analogues in medicinal chemistry
occurrence, synthesis and biological activity”. Curr Med Chem.2005; 12(8):887-916.
2) Curini M, Cravotto G, et al. “Chemistry and biological activity of natural and
synthetic prenyloxycoumarins.” Curr Med Chem.2006; 13(2):199-222.
3) Kulkarni MV, et al. “Recant advance in coumarins and 1-azacoumarins as versatile
biodynamic agent.” Curr Med chem. 2006; 13(23):2795-818.
4) Hoult JR, Paya M. “Pharmacological and biochemical action of simple coumarins:
natural product with therapeutic potential.” Gen pharmacology. 1996; 27(4):713-722.
5) Litina dj, et al. “Natural and synthesis coumarin derivative with anti-inflammatory
/antioxidant activities.” Curr Pharm. Des. 2004; 10(30):3813-3833.
6) Kostova I. “coumarins as inhibitor of HIV reverse transcriptase.” Curr HIV Res.
2006; 4(3):347-63.
7) Barnard Dale L .et al. “Coumarins and pyranocoumarines, pontential novel
pharmacophores for inhibition of measles virus replication.” 2002; 13:1:39-59.
8) Weber us, et al. “Antitumor activities of coumarin, 7-hydroxy coumarin and its
glucuronide in several human tumor cell lines.” Res. Commun Mol pathol
pharmacology. 1998; 99(2):193-206.
9) Kostova I. “Synthetic and natural coumarins as cytotoxic agent.” Curr Med Chem.
Anticancer agent. 2005; 5(1):29-46.
10) Manvar et al. “Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin 4-acetic acid benzlidene hydrezide.” Eur J Med chem. 2008; 43(11):2395-403.
11) Nancy E. lem, et al. “Antiviral activity of N-Etylisatin B-thosemicarbazone in
vaccinia infected mice.” The journal of immunology, 1965; 94:794-804.
12) Bauer, D.J. et al. “The structure activity relationships of antiviral chemotherapeutic
activity of isatin ?- thiosemicabazones.” Datos del recurso.
13) Surendra P. singh, et al. “Synthesis of some new substituted thiosemicarbazides as
potential antiviral agent.’’ Journals of Archiv der Pharmazia 2006; 316(10):817-821.
14) Koti rajesh, S. et al. “Synthesis and evaluation of the antibacterial and antitubercular
activity of some N1-aral-N4–(3-chloro-4-fluorophenyl)thiosemicabazones and copper
Complexes.” Arzneimittel-forschung 2005; (2):107-113.
15) Agarwal, et al. “ Synthesis and anti amoebic activity of metronidazole
thiosemicarbazones analogues.” European Journal of medical chemistry.” 2008;
43(9):2035-2039.
16) Weizhou, xi- Wen et al. “Synthesis and anticancer activity of thosemicarbazone.”
Bioorganic & medicinal chemistry letters.” 2006; 16(8):2213-2218.
17) Ahmed M.M., El-saghier et all. “Synthesis and antibacterial activity of some new
fused chromenes. ” ARKIVOC. 2007; 16: 83-91.
18) Banjamin Prescott. “4-Hydroxy 2-butenone thiosemicarbazones a pontecial
anticancer agent.” Journal of medicinal chemistry.1967; 10(3):484-485.
19) M.S.More, et al. “Synthesis, characterization, antioxidant and antimicrobial activity
of different heterocycle derived from 3-formyl chrimones.” Oriental journal of
chemistry 2007; 23:329-334.
20) R.Suthakaran, M.Bhagavan.,S.Kavimani1, et al. “Synthesis, Antioxidant, Antimicrobial activity of [2-(5-substituted aryl 1- N-substituted aryl amino methyl)
pyrazol-3-yl] benzofuran.” Rasayan Journal of chemistry. 2008 1:1:39-45.
21) Y. Rajendra Prasad .,P.Ravikumar., “Synthesis and antimicrobial activity of some
novel chalcones of 2-hydroxy -1-Acetonapthone and 3-acetyl coumarin.” Journal of
chemistry 2006; 3:13:236-241.
22) Vijayananda Krishna Revankar., Ph.D. Thesis on “Chemistry of some Coordination
Compounds”. Submitted to Karnatka university Dharwad., 1988; 114-115 .
23) A.I.Vogel, “A Text Book of Practical Organic Chemistry”., ELBS, 4TH Edition ,
802pp.
9
Signature of Candidate
10
Remarks of the guide
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.
(MR.NITIN PATEL)
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.
Dr. B.H.M. JAYAKUMAR SWAMY
Professor,
P.G. Dept. of Pharmaceutical
Chemistry,
S.C.S College of Pharmacy,
Harapanahalli-583131.
Davanagere-Dist.
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
Dr. B.SHIVAKUMAR
Professor,
P.G. Dept. of Pharmaceutical
Chemistry,
S.C.S College of Pharmacy,
Harapanahalli-583131.
Davanagere-Dist.
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.
Dr. E. JAYACHANDRAN
Professor and Head.
P.G. Dept. of Pharmaceutical
Chemistry,
S.C.S College of Pharmacy,
Harapanahalli-583131.
Davanagere-Dist.
11.6 Signature
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12.1 Remarks of the Principal
12.2 Signature
(Dr. S. RAMACHANDRA.SETTY)