title: Design, synthesis, and antitubercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs.
abstract: Twenty-eight newer 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs were synthesized by microwave irradiation method and evaluated for in-vitro and in-vivo antitubercular activity against multidrug-resistant M. tuberculosis stains. Structure-activity relationship study was carried out and found NO(2) (o) substituted 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin was most potent antitubercular agent against M. tuberculosis, even better than standard drug isoniazid and comparable with rifampin. Other synthesized compounds 7j, 7f, 7a, 7e and 5d, 5f were found moderate to good activity in in-vitro model at lower IC(50) values 85 microM, 154 microM, 157 microM, 164 microM, 170 microM and 190 microML respectively. In in-vivo animal model compound 7j was drastically reduced the bacterial load in lung and spleen tissues at the dose of 25 mg/kg body weight.
authors.affiliation: Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad 382 481, Gujarat, India. k_manna2002@yahoo.com
authors.forename: Kuntal
authors.initials: K
authors.lastname: Manna
authors.forename: Yadvendra K
authors.initials: YK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D015195:Drug Design; D018432:Drug Resistance, Multiple; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D001572:Benzofurans; C105430:benzofuran