Design, Synthesis, Anti-Tubercular Evaluation and Teratogenicity Studies of Furanyl Pyrazolo[3,4-b] Quinoline-5-Ones

We have synthesized novel pyrazolo-quinoline analogues (P1–10) in an effort to create newer antitubercular drugs against the rising bacterial resistance. NMR, IR and ESI-MS spectra were utilized to characterize the synthesised compounds. The antitubercular activity of the target compounds was evaluated against Mycobacterium tuberculosis. Six derivatives (P1–6) displayed very significant activity at 1.6 µg/mL concentration and were found to be more active than pyrazinamide standard. Thus, as per the drug susceptibility results the MIC value could be considered between 1.6 and 0.8 µg/mL. In addition, all the synthesised compounds were subjected to molecular docking studies against specific protein, Enoyl acyl carrier protein reductase (InhA) in complex with N-(4-methylbenzoyl)-4-benzylpiperidine, PDB ID: 2NSD. Among all the compounds the most effective compounds were found an Autodock score of 11.6 and 11.2 against 2NSD, respectively. Further, Zebrafish larvae have been used to test the teratogenicity of the synthesised compounds. There were no indications of abnormalities with (P2), (P4), (P5), (P6), and (P10) at 0.5 µM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1134/S1068162023010053.