Title:Synthesis, Docking Studies, and Biological Evaluation of Betti Bases as
Promising Anti-tubercular Agents
Volume: 20
Issue: 6
Author(s): Poornima Acharya, Mucheli Muni Venkata Ramana*, Nilesh Korgavkar, Ganesh Pavale and Manish Upadhyay
Affiliation:
- Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai, 400 098, India
Keywords:
Betti bases, docking studies with InhA, microplate alamar blue assay (MABA), neutrophil function test (NFT), in vitro cytotoxicity assay, drug resistant.
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.