Isoniazid-Dihydropyrimidinone Molecular Hybrids: Design, Synthesis, Antitubercular Activity and Cytotoxicity Investigations with Computational Validation.

In this study, we designed and synthesized a new series of  isoniazid-dihydropyrimidinone molecular hybrids (8a-8n). All compounds were structurally characterized using spectroscopic techniques viz., FTIR, NMR (1H, 13C, HMBC, and HSQC), and HRMS followed by their in vitro anti-tubercular evaluation including their precursors (4a-4n), and a standard anti-tubercular drug (Isoniazid; INH).

The Emerging Landscape of Tubercular Targets: A Medicinal Chemistry Approach.

Antitubercular drug discovery progress in the last decade, especially research on the biological function, target inhibition and diagnosis of tuberculosis (TB) diagnosis has considerably advanced. The application of target-based drug discovery techniques have become a more powerful tool for medicinal chemists in developing new therapeutic strategies, such as its application in the identification/validation of new targets, new leads, and drug candidates with optimized efficacy. This has been further evidenced by the recent approval of delamanid and bedaquiline for the treatment of MDR-TB and XDR-TB, respectively.

Design and Evaluation of Quinoline-Schiff Bases Targeting Mtb DNA Gyrase: In Vitro and Computational Approaches.

A new series of quinoline-Schiff bases was designed and synthesized using a straightforward and efficient methodology involving the condensation of 2-chloroquinoline-3-carbaldehyde with substituted aromatic amines. A total of 17 quinoline-Schiff bases were synthesized with 56%-86% yields and characterized by using H NMR, C NMR, and high-resolution mass spectra (HRMS) as potent anti-mycobacterial agents with Mtb DNA gyrase inhibitory activity. Among all, compound 7f displayed a significantly potent broad-spectrum antitubercular and antimicrobial activity against most of the tested strains of bacteria and fungi, with minimum inhibitory concentration (MIC) values in the range of 1.