jrnls.org logo
Submit

BROWSE ALL JOURNALS

SEE ALL 19 JOURNALS
Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

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

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★ Corresponding author

  1. 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
  2. 2Department of Biotechnology and Food Technology, Durban University of Technology, Durban, SOUTH AFRICA.
  3. 3Institute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences (NCBS), TIFR, GKVK, Bellary Road, Bangalore, Karnataka, INDIA.
  4. 4Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, KINGDOM OF SAUDI ARABIA.
  5. 5Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban, SOUTH AFRICA.
  6. 6Faculty of Pharmacy, Philadelphia University, Amman, JORDAN.
  7. 7Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, EGYPT.

CORRESPONDENCE

Katharigatta N. Venugopala

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

kvenugopala@kfu.edu.sa

Received: 12-03-2019; Revised: 29-04-2019; Accepted: 13-05-2019.

Volume 53, Issue 3 · pp. 545–552 · PUBLISHED 2019 · DOI: 10.5530/ijper.53.3.87

View on IJPER original site ↗

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-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.

KEYWORDS

Open in new tab

REFERENCES

As published

Showing references and in-text citations exactly as published.

    Cite this article

    SELECT FORMAT

    Venugopala, K. N., Tratrat, C., Chandrashekharappa, S., Attimarad, M., Sreeharsha, N., Nair, A. B., Pottathil, S., Venugopala, R., Al-Attraqchi, O. H. A., Morsy, M. A., Haroun, M., & Odhav, B. (2019). Anti-tubercular Potency and Computationallyassessed Drug-likeness and Toxicology of Diversely Substituted Indolizines. Indian Journal of Pharmaceutical Education and Research, 53(3), 545–552. https://doi.org/10.5530/ijper.53.3.87