Development of 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis.

Abstract

InhA, the enoyl acyl carrier protein reductase of Mycobacterium tuberculosis (MTB) is an attractive target for developing novel anti-tubercular agents. Twenty eight 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives were synthesized and evaluated for their in vitro MTB InhA inhibition. Compounds were further evaluated for their in vitro activity against drug sensitive and resistant MTB strains and cytotoxicity against RAW 264.7 cell line. Compounds were docked at the active site of InhA to understand their binding mode and differential scanning fluorimetry was performed to ascertain their protein interaction and stability.

• Authors: Ganesh S Pedgaonkar, Jonnalagadda Padma Sridevi, Variam Ullas Jeankumar, Shalini Saxena, Parthiban Brindha Devi, Janupally Renuka, Perumal Yogeeswari, Dharmarajan Sriram
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 86 Pg. 613-27 (Oct 30 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 25218910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• 2-(4-oxoquinazolin-3(4H)-yl)acetamide
• Acetamides
• Bacterial Proteins
• Enzyme Inhibitors
• Quinazolines
• Oxidoreductases
• InhA protein, Mycobacterium

Topics

• Acetamides (chemical synthesis, chemistry, pharmacology)
• Animals
• Bacterial Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Mice
• Microbial Sensitivity Tests
• Molecular Docking Simulation
• Molecular Structure
• Mycobacterium tuberculosis (drug effects, enzymology)
• Oxidoreductases (antagonists & inhibitors, genetics, metabolism)
• Quinazolines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tuberculosis (drug therapy)