title: Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents.
abstract: In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential.
authors.affiliation: Department of Pharmacy, Mangalayatan University, Aligarh, UP, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Garg
authors.affiliation: School of Pharmacy, People's University, Bhopal, MP, India.
authors.forename: Milind
authors.initials: M
authors.lastname: Pande
authors.affiliation: 728 HMRC, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Canada.
authors.forename: Ambika
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, AB T6G 2S2, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: 728 HMRC, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Canada. Electronic address: rkumar@ualberta.ca.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009163:Mycobacterium bovis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: C000612895:4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one; C000612897:4-amino-5-heptynylpyrimidine-2(1H)-one; D000900:Anti-Bacterial Agents; D011744:Pyrimidinones
keywords: Anti-mycobacterial agent; Heterocycles; Pyrimidines; Tuberculosis