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Published on:April 2019
Indian Journal of Pharmaceutical Education and Research, 2019; 53(2s):s121-s128
Original Article | doi:10.5530/ijper.53.2s.56

Anti-tubercular Potency and Computationally assessed Drug-likeness and Toxicology of Diversely Substituted Indolizines


Authors and affiliation (s):

Katharigatta N. Venugopala1,2,*, Christophe Tratrat1, Sandeep Chandrashekharappa3, Mahesh Attimarad1, Nagaraja Sreeharsha1, Anroop B. Nair1, Shinu Pottathil4, Rashmi Venugopala5, Omar Husham Ahmed Al-Attraqchi6, Mohamed A. Morsy1,7, Michelyne Haroun1, Bharti Odhav2

1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.

2Department of Biotechnology and Food Technology, Durban University of Technology, Durban, SOUTH AFRICA.

3Institute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences (NCBS), TIFR, GKVK, Bellary Road, Bangalore, Karnataka, INDIA.

4Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.

5Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban, SOUTH AFRICA.

6Faculty of Pharmacy, Philadelphia University, Amman, JORDAN.

7Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.

Abstract:

Background: Several promising compounds against multi-drug-resistant Mycobacterium tuberculosis (MTB) are currently in the drug discovery and development pipeline. While it has yet to establish candidature in this pipeline, early results have been promising for the putative anti-mycobacterial potency of the indolizine scaffold. Methods: The molecular properties, as well as the Absorption, Disruption, Metabolism, Excretion and Toxicity (ADMET) of indolizines were assessed using the Accelry's Discovery Studio 4.0 client package. Results: The current study evaluated the in vitro potency of 14 diversely substituted indolizine congeners against H37Rv and multi-drug-resistant strains of M. tuberculosis. While all 14 congeners showed potent anti-mycobacterial activity, only three of them had optimal drug-likeness and toxicology, as per in silico evaluations. Conclusion: The results of the current study identify three indolizine congeners (ethyl 2-methyl-3-(4-methylbenzoyl) indolizine-1-carboxylate (1b)), ethyl 7-acetyl-3-benzoyl- 2-methylindolizine-1-carboxylate (3a) and ethyl 7-acetyl-3-benzoyl-2-ethylindolizine-1- carboxylate (3b) with good anti-mycobacterial potency and acceptable drug-likeness and toxicity profiles. Furthermore, the study narrows down the list of indolizine congeners for further evaluation and underscores the importance of computational tools in mitigating the over-utilization of resources and associated costs of drug discovery.

Key words: Multi-drug resistant Mycobacterium tuberculosis, in-silico, Indolizine, Druglikeness, Pharmacokinetics, Toxicity.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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