Chemical synthesis, molecular modeling and pharmacophore mapping of new pyrrole derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth

Substituted phenylthiazolyl benzamide and pyrrolyl benzamide derivatives were developed using molecular hybridization technique to create novel lead antimycobacterial molecules used to fight against Mycobacterium tuberculosis . The newly synthesized molecules have inhibited InhA, the enoyl-ACP reduc...

Full description

Saved in:
Bibliographic Details
Published in:Medicinal chemistry research 2019-11, Vol.28 (11), p.1838-1863
Main Authors: Joshi, Shrinivas D., Kumar, S. R. Prem, Patil, Sonali, Vijayakumar, M., Kulkarni, Venkatarao H., Nadagouda, Mallikarjuna N., Badiger, Aravind M., Lherbet, Christian, Aminabhavi, Tejraj M.
Format: Article
Language:English
Subjects:
Benzamide
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Chemical bonds
Chemical Sciences
Chemical synthesis
Derivatives
Enzymes
Fatty acids
Hybridization
Inhibitors
Mapping
Molecular modelling
NAD
Organic chemistry
Original Research
Pharmacology/Toxicology
Reductase
Reductases
Tuberculosis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Substituted phenylthiazolyl benzamide and pyrrolyl benzamide derivatives were developed using molecular hybridization technique to create novel lead antimycobacterial molecules used to fight against Mycobacterium tuberculosis . The newly synthesized molecules have inhibited InhA, the enoyl-ACP reductase enzyme from the mycobacterial type II fatty acid biosynthetic pathway. Of these, compound 3b showed H-bonding interactions with Tyr158 and co-factor NAD + that binds the active site of InhA. All the molecules were screened for in vitro antitubercular activity against M. tuberculosis H 37 Rv, as well as some representative molecules as the inhibitors of InhA. Thirteen compounds exhibited good anti-TB activities (MIC = 1.6 μg/mL), but only few representative molecules showed the moderate InhA enzyme inhibition activity. Basic core moiety and docked mode of all the synthesized compounds inside the proposed binding pocket of InhA with the final selected pharmacophore model molecular alignment for InhA receptor ligands.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-019-02418-1