Anti-tubercular Potency and Computationallyassessed Drug-likeness and Toxicology of Diversely Substituted Indolizines
Indian Journal of Pharmaceutical Education and Research
Katharigatta N. Venugopala1Department 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.
Christophe Tratrat1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Sandeep Chandrashekharappa3Institute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences (NCBS), TIFR, GKVK, Bellary Road, Bangalore, Karnataka, INDIA.
Mahesh Attimarad1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Nagaraja Sreeharsha1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Anroop B. Nair1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Shinu Pottathil4Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Rashmi Venugopala5Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban, SOUTH AFRICA.
Omar Husham Ahmed Al-Attraqchi6Faculty of Pharmacy, Philadelphia University, Amman, JORDAN.
Mohamed A. Morsy1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA., 7Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.
Michelyne Haroun1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
Bharti Odhav2Department of Biotechnology and Food Technology, Durban University of Technology, Durban, SOUTH AFRICA.
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-benzoyl2-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.
