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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Synthesis, Docking Studies, and Biological Evaluation of Betti Bases as Promising Anti-tubercular Agents

Author(s): Poornima Acharya, Mucheli Muni Venkata Ramana*, Nilesh Korgavkar, Ganesh Pavale and Manish Upadhyay

Volume 20, Issue 6, 2023

Published on: 03 September, 2022

Page: [724 - 737] Pages: 14

DOI: 10.2174/1570180819666220520141039

Price: $65

Abstract

Background: The occurrence of Tuberculosis (TB) has significantly increased worldwide. The extensively drug-resistant tuberculosis (XDR-TB) and multi-drug resistant tuberculosis (MDR-TB) have made it more challenging to treat this mycobacterial infection caused by the Mycobacterium tuberculosis MTB-H37Rv strain. The present treatments for tuberculosis are of long duration and with side effects. Thus, it is necessary to discover new drugs with short-term chemotherapy, fewer health hazards, and cost effectiveness.

Objective: The objective of the study was to divulge the antitubercular properties of Betti base scaffolds.

Method: Betti bases were designed, synthesized 4a-4h, 6a-6h, and investigated for their in vitro antitubercular activity using Microplate Alamar Blue assay (MABA) against the MTB-H37Rv strain. Their binding affinity with amino acids was studied by performing molecular docking studies using InhA (PDB ID: 2NSD) present in the MTB-H37Rv strain. Cytotoxicity assay and neutrophil function test (NFT) were also performed.

Results: The Betti bases (4a-4h, 6d) showed minimum inhibitory concentration (MIC) values ranging from 1.6 μg/mL to 6.25 μg/mL against the MTB-H37Rv strain. The compounds (4a-4h, 6a-6h) were investigated for their ADME properties and good pharmacokinetic profiles were observed. In molecular docking studies, a strong binding affinity between InhA and the compounds (4a-4h, 6a-6h) was observed, which provided theoretical insight into the inhibitory action of the synthesized compounds (4a-4h, 6a-6h) against InhA. NFT of the compounds (4a-4h, 6a-6h) showed no harmful effects on the functions of neutrophils. In vitro cytotoxicity assay against Vero cell lines revealed the non-cytotoxic behavior of the compounds.

Conclusion: Betti bases can be considered to be a promising class of molecular entities that can lead to the development of new anti-tubercular leads.

Keywords: Betti bases, docking studies with InhA, microplate alamar blue assay (MABA), neutrophil function test (NFT), in vitro cytotoxicity assay, drug resistant.

Graphical Abstract

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