Isoflavonoid and Furanochromone Natural Products as Potential DNA Gyrase Inhibitors: Computational, Spectral, and Antimycobacterial Studies

[Image: see text] In pursuit of new antitubercular agents, we here report the antimycobacterial (H(37)Rv) and DNA gyrase inhibitory potential of daidzein and khellin natural products (NPs). We procured a total of 16 NPs based on their pharmacophoric similarities with known antimycobacterial compounds. The H(37)Rv strain of M. tuberculosis was found to be susceptible to only two out of the 16 NPs procured; specifically, daidzein and khellin each exhibited an MIC of 25 μg/mL. Moreover, daidzein and khellin inhibited the DNA gyrase enzyme with IC(50) values of 0.042 and 0.822 μg/mL, respectively, compared to ciprofloxacin with an IC(50) value of 0.018 μg/mL. Daidzein and khellin were found to have lower toxicity toward the vero cell line, with IC(50) values of 160.81 and 300.23 μg/mL, respectively. Further, molecular docking study and MD simulation of daidzein indicated that it remained stable inside the cavity of DNA GyrB domain for 100 ns.