1
Rajiv Gandhi University Of Health Sciences, Karnataka
Bangalore
Proforma For Registration Of Subjects For Dissertation
1. / Name of the candidate and address / AMIT SAXENAK.L.E.S’s COLLEGE OF PHARMACY
2nd BLOCK, RAJAJINAGAR,
P.B. NO. 1062,
BANGALORE-560010.
PERMANENT ADDRESS
K.L.E.S’s COLLEGE OF PHARMACY2nd BLOCK, RAJAJINAGAR,
P.B. NO. 1062,
BANGALORE-560010.
2. / Name of the institution / K.L.E.S’s COLLEGE OF PHARMACY,
2nd BLOCK, RAJAJINAGAR,
P.B. NO. 1062,
BANGALORE-560010
3. / Course of study and subject / MASTER OF PHARMACY -
PHARMACEUTICAL CHEMISTRY
4. / Date of admission / 25-05-20075. / Title of the Topic / “SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF SOME NEW INDOLE DERIVATIVES”.
6. / Brief resume of the intended work:
6.1 Need for the study:
The synthetic versatility of indole derivatives such as isatin has led to the extensive use of these compounds in organic synthesis, which stemmed the interest in the biological and pharmacological properties of its derivatives.1 Mono and bis hydrazone derivatives of indole find wide application due to their anti bacterial tuberculostatic and fungicidal properties.2 The schiff and mannich bases of isatin derivatives, demonstrated good anti bacterial and anti fungal activities.3 Antiproliferative and proapoptotic actions of 5- hydroxy indole and isatin derivatives have been described for different tumor cells.4
Prompted by these results we have planned to synthesize new series of indole derivatives in order to screen for antimicrobial activity on gram-positive and gram-negative bacteria and selected strains of fungi.
6.2 Review of Literature:
An extensive literature review has been made on the subject. Numerous reports have been found on the synthesis of indole and its derivatives for different pharmacological actions.
Omar et al.5 have synthesized derivatives of indole and screened for antiviral and antimicrobial activities. Similarly Joshi et al.6 and Sridhar et al.7 screened the same for antibacterial activity and Karali et al.8 and Ali et al.9 synthesized indole derivatives for antimicrobial activity.
Besides this indole derivatives have shown their promising effects as cytotoxic agents10, in breast cancer11, antileukemic activity12, antitubercular13, anti convulsant 14 and CNS activities15.
Derivatives of indole have also been evaluated for the suppression of myocardial ischemic injury16 and anti HIV (a nobel protease inhibitor)17,18 and the newer amino pyrimidimino analogues have been found as novel non transcriptase inhibitors for the HIV and other opportunistic infection of AIDS.
This review of literature indicates that indole and its derivatives have the potential for the research and development in the field of medicinal chemistry especially for anti microbial activity.
6.3 Objective Of The Study:
1. To carry out literature review and survey of indole compounds.
2. To establish the methods of synthesis for the proposed compounds.
3. To synthesize indole and their derivatives by appropriate method.
4. To confirm the structure of synthesized compounds by spectral and elemental analyis.
5. To evaluate the proposed compounds for anti-microbial activity by the known standard methods.
7. / Materials And Methods:
7.1 Source of data:
Compact disc:
§ International Pharmaceutical Abstract 1970-2006.
§ Web sources and e-journals.
§ Chemical abstract.
§ Analytical abstract.
Journals:
§ Indian Journal of Medicinal Chemistry.
§ Indian Journal of Pharmaceutical Science.
§ Journal of Medicinal Chemistry.
§ Journal of Organic Chemistry.
§ Chemical Pharmaceutical Bulletin.
§ European Journal of Medicinal Chemistry.
7.2 Method of collection of data:
· Synthesis: The proposed indole and their derivatives will be synthesized by using appropriate methods described in the literature.
· Purification and physical constants: The physical parameters like solubility in various solvents, melting point/boiling point, nature of crystals – purification is done by re-crystallization in a suitable solvent.
· Spectral verification: FTIR, mass spectra, 1H-NMR.
· Chromatographic Technique: By using TLC and combining physical and spectral data, one can confirm the structure of target compound.
· Biological Activity: The synthesized compound will be evaluated for its anti-microbial 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.
7.4 Has Ethical Clearance Been Obtained From Your Institution In
Case of 7.3?
NOT APPLICABLE.
8. List of References:
1. Da Silva JF, Garden SJ, Pinto AC. The chemistry of isatin. A review from 1975 to 1999. J Braz. Chem Soc 2001;2(3):273-324.
2. Samus NM, Burdenko TA, Gylka VV, Tsapkov VI. Synthesis and characterization of Co, Ni, Cu and Zn complexes with 3-salicylidenehydrazone-2-indolinone. J Chem Pharma 1994;12:40.
3. Pandeya SN, Sriram D, Nath G, Declereq E. Synthesis of 3,3 methylene bis (3,1,phenylenenitrilo) bis (1,3,di hydro) 2H indole-2-one as a novel bis schiff base. Eur J Pharm Sci 1999;9:25.
4. Cane A, Tournaire MC, Barritault D, Crumeyrolle-Arias M. Inhibition of brain mitochondrial mono amine oxidases by the endogeneous compound 5-hydroxyoxindole. Biochem Biophys Res Commun 2000;276:379.
5. Omar AM, Eshba NH, Salama HM. Synthesis of some substituted isatin b-thiosemicarbazones and isatin b-hydrazonothiazoline derivative as potential anti-viral and anti-microbial agents. Arch Pharm (Weinheim) 1984 Aug;8:317.
6. Joshi C, Dandia A, Bhagat S. Synthesis, 19F NMR spectral studies and antibacterial evaluation of some new fluorine containing indole derivatives. Journal of fluorine chemistry 1990 Jun 15;48:169-88.
7. Sridhar SK, Saravanan M, Ramesh A. Synthesis and antibacterial screening of hydrazones schiff and mannich bases of isatin derivatives. Eur J Med Chem 2001 Jul-Aug;36(7-8):615-25.
8. Karali N, Terzioglu N, Gursoy A, Otuk G, Kiraz M, Yogenoglu Y. New 4- thiazoline-2-hydrazono-1H-2-indolinones as possible antimicrobial agents. Boll chim farm 1998 March;137(3):63-8.
9. Ali S, Alam M. Potential antimicrobial agents –structural modifications and antimicrobial activity of some isatin derivatives. Arch Pharm Res 1994 Apr;17(2):131-3.
10. Yogeeswari P, Sriram D, Kavya R, Tiwari S. Synthesis and in vitro cytotoxic evaluation of mannich bases. Biomed pharmacotherapy 2005;59:501-10.
11. Carn EJ, Liu BD, Bjeldanes LF, Firestone GL. Indole derivative as novel breast cancer therapy. Journal of biological chemistry 2001;276(25):22332-40.
12. Eshba NH, Salama HM. Synthesis and evaluation for anti-leukemic activity of 5-(2-oxo-3-indolinylidene)thiazolidene-2,4-dione-1,3-di-mannich bases derivatives. Pharmazie 1985 May;40(5):320-22.
13. Pandeya SN, Sriram D, Yogeeswari P, Authan S. Anti tubercular activity of norfloxacin mannich bases with isatin derivative. International journal of experimental and clinical chemotherapy 2001;47(4):266-9.
14. Pandeya SN, Raja AS, James PS. Synthesis of isatin semicarbazones as novel anticonvulsant-role of hydrogen bonding. Journal of pharmaceutical science 2002;5(3):266-71.
15. Singh TJ, Gujral PK. Neuro pharmacological action of isatin. Indian journal of pharmacology 1971;3(4):187-91.
16. Chapman JG, Magee PW, Stukenbrok HA, Beckius GE, Milice AJ, Tracey WR. A novel non-peptidic capase-3/7 inhibitors, (s)-(+)-5[1-(2-methoxy methyl pyrolidinyl)sulfonyl] isatin reduces myocardial ischemic injury. European Journal of Pharmacology 2002;456(1-3):59-68.
17. Sriram D, Bal TR, Yogeeswari P. Newer amino-pyrimidinoisatin analogs as novel non reverse transcriptase inhibitor for the HIV and other opportunistic infection of AIDS, design synthesis and biological evaluation. Formaco 2005;60:384.
18. Ghosh AK, Schlitz G, Perali RS, Leshcheuko S, Kay S, Walters DE, et al. Design and synthesis of novel HIV-1 protease inhibitors incorporating oxy indoles as the p2 ligands. Bioorganic and medicinal chemistry letters 2006;16(7):1869- 73.
9. / Signature of the candidate
10. / Remarks of the guide / Recommended
11. / Name and Designation of
11.1 Guide / Dr.V.C.YeligarAssistant Professor
Dept. of Pharmaceutical Chemistry,
K.L.E.S’s College of Pharmacy,
Rajajinagar, Bangalore-10
Annexure-II (Approved Guide Letter enclosed)
11.2 Signature
11.3 Head of the Department / Prof. Y.D.Satyanarayana
Vice Principal
Head of the Department,
Dept. of Pharmaceutical Chemistry.
K.L.E.S’s College of Pharmacy,
Rajajinagar, Bangalore-10.
11.4 Signature
12. / 12.1 Remarks of the Chairman and
Principal / Recommended for registration
12.2 Principal / Dr. Purnima Ashok
Principal,
K.L.E.S’s College of Pharmacy,
2nd block, Rajajinagar,
Bangalore-10.
12.3 Signature