IJCRR

IJCRR - 4(22), November, 2012

Pages: 151-156

QSAR STUDIES OF PHTHALIMIDE DERIVATIVES FOR THEIR POTENT ANXIOLYTIC ACTIVITY

Author: Suvarna Prabhakar Gajare, Supriya S. Mahajan

Category: Healthcare

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Abstract:

Heterocyclic compounds represent an important class of biologically active molecules; specifically those containing the substituted imide nucleus have been shown to possess high biological activities. Phthalimide derivatives have been found to exhibit industrial, agricultural and biological applications. A series of phthalimide derivatives were synthesized and studied for their acute oral toxicity as per the OECD guidelines and anxiolytic activity using Elevated plus-maze animal model. The compounds were screened for anxiolytic activity using diazepam as the standard. Anxiolytic activity was calculated based on the per cent open arm entries and average time spent by mice on open arms. The QSAR studies were carried out by using molecular modeling software Maestro from Schrodinger, USA. The best QSAR model was obtained when anxiolytic activity was correlated with ionization potential (IP) values of phthalimide derivatives.

Keywords: Phthalimides, Acute oral toxicity, Anxiolytic activity, Elevated plus maze, QSAR, Ionization potential

References:

1. Antunes R, Batista H, Srivastava R, Thomas G, Araujo CC, Longo RL. Synthesis, characterization and interaction mechanism of new  oxadiazolo-phthalimides as peripheral analgesics. J Mol Str 2003; 660:1-13.

2. Bailleux V, Vallee L, Nuyts JP, Vamecq J. Anticonvulsant activity of some 4-amino-Nphenylphthalimides and N-(3-amino-2- methylphenyl) phthalimides. Biomed and Pharmacother 1994; 48:95-101.

3. Jean SL, Paulo YR, Chung CM, Celio TH, Fernando PR, Clarice LQ. Synthesis and in vitro anti mycobacterium tuberculosis activity of a series of phthalimide derivatives, Bioorg Med Chem 2009;17:3795–3799.

4. Babu AH, Ramana AV, Sinha R, Yahav JS, Arora SK, Antitubercular agents. Part 1: Synthesis of phthalimido and naphthalimido linked phenazines as a new prototype antitubercular agent. Bioorg Med Chem 2005;15:1923-1926.

5. Chapman JM, Cocolas GH, Hall IH, Hypolipidemic activity of phthalimide derivatives. A comparison of phthalimide and 1,2-benzisothiazolin-3-one 1,1-dioxide derivatives to phthalimidine and 1,2- benzisothiazoline 1,1-dioxide congeners. J Med Chem 1983;26 (2):243–246.

6. Hassanzadeh F, Rabbani M, Khodarahmi GA, Fasihi A, Hakimelahi GH, Mohajeri M, Synthesis of phthalimide derivative and evaluation of their anxiolytic activity, Res Pharm Sci 2007; 2: 35-41.

7. Collin X, Robert J, Wielgosz G, Le BG, Bobin-Dubigen C, Grimaud N. New antiinflammatory N-pyridinyl (alkyl) phthalimides acting as tumour necrosis factor-alpha production inhibitors. Eur J Med Chem 2001;36:639 -649.

8. Patel HS, Mistry HJ, Patel NK, Desai SN. Synthesis and antimicrobial activity of some new phthalimide derivatives. Bulgarian Chem Comm 2004;36:167 -172.

9. Al-Rashood KA, Mustafa AA, Alhaider AA, Ginawi OT, Madani AAE, El-Obeid HA. Antipsychotic properties of new N-(4- substituted-1-piperazinylethyl) and N-(4- substituted-l-piperidinylethyl)-phthalimides. J Pharm Sci 1988;77: 898-901.

10. Tripathi, KD. Essentials of medicinal pharmacology. 4th ed. New Delhi: Jayee brother publication; 1993. p.752.

11. Koslow SH, Murthy R, Coelho, GV. Plants and plant products for mental health, us department of health and human services, 4th edition, 1995, 163-171.

12. Kubinyi H. Burger?s medicinal chemistry and drug discovery: the quantitative analysis of structure activity relationships, 5th ed. New York: John Wiley and Sons; 1995(1) p. 497- 552.

13. Mure SA, Bologab CM, Mracecb A, Chiriacb B, Jastorffc ZS, Náray-Szabóe G. Comparative QSAR study with electronic and steric parameters for cAMP derivatives with large substituents in positions 2, 6 and 8, J Mol Str: Theochem 1995;342: 161-171.

14. Gajare SP, Mahajan SS. Eco-Friendly synthesis of phthalimide derivatives, their analgesic activitiy and QSAR studies. I J Pharm Phytopharmacological Res. In press

15. OECD (2008) OECD Guidelines for the Testing of Chemicals Test No. 425: Acute Oral Toxicity – Up and Down procedure.

16 Sharma K, Arora V, Rana AC, Bhatnagar M. Anxiolytic effect of convolvulus pluricaulis choisypetals on elevated plus maze model of anxiety in mice. J Herb Medi Toxi 2009;3: 41-46.

17 http://www.answers.com/topic/anxiolytic activity - animal model, visited on December 2010.

18 Kulkarni SK. Handbook of experimental pharmacology, 3rd ed. New Delhi: Vallabh Prakashan 1999; p. 27-32, 123-128.