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

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 NO2 (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 IC50 values 85 μM, 154 μM, 157 μM, 164 μM, 170 μM and 190μML 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.

In in-vivo animal model, test drugs (7j, 7f, 7a, 5d, 5f) has drastically been reduced bacterial counts in mice lungs and spleen tissues, which comparable with INH and Rifampin.Figure optionsDownload as PowerPoint slide