title: 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.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Pedgaonkar
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Variam Ullas
authors.initials: VU
authors.lastname: Jeankumar
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Parthiban Brindha
authors.initials: PB
authors.lastname: Devi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Janupally
authors.initials: J
authors.lastname: Renuka
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, A.P. 500078, India. Electronic address: drdsriram@yahoo.com.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: C000598945:2-(4-oxoquinazolin-3(4H)-yl)acetamide; D000081:Acetamides; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011799:Quinazolines; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium
keywords: Cytotoxicity; Enoyl acyl carrier protein reductase; InhA; Tuberculosis