Synthesis and Antitubercular Activity of Novel 1,5-Naphthyridin-2(1H)-one based Carbohydrazide Derivatives

A library of novel 1,5-naphthyridin-2(1H)-one based carbohydrazide derivatives (6a-j) were synthesized involving functional group interconversion, esterification and coupling reactions. All the newly synthesized carbohydrazide derivatives (6a-j) were evaluated for their ability to inhibit the growth of M. tuberculosis mc26230 by determining their minimum inhibitory concentration (MIC), with rifampicin used as the standard reference. Compound 6f (3-cyano) displayed potent activity with a MIC value of 4 µg/mL, compound 6g (4-cyano) displayed activity with an MIC value of 8 µg/mL, whereas the ortho-substituted cyano compound 6e showed activity a little lower with MIC of 16 µg/mL. Whereas all other compounds displayed good to moderate activity. The molecular docking study of potent compound 6f against crystal structure of dihydrofolate demonstrated a significant docking score and binding interactions in support of experimental investigations.