Journal of Theoretical & Computational Science
Open Access
ISSN: 2376-130X
ISSN: 2376-130X
Archana Kapoor* and Mithlesh Yadav
The indazole scaffold has gained prominence in medicinal chemistry due to its diverse biological activities and potential as a pharmaceutical agent. This study delves into the design, synthesis and comprehensive evaluation of indazole derivatives, aiming to develop effective anticancer, antioxidant and antimicrobial agents. A series of computational studies, including molecular docking and Quantitative Structure–Activity Relationship (QSAR) analysis, guided the design of potent Tyrosine Threonine Kinase (TTK) inhibitors. The 2D-QSAR model (r²=0.9512) and 3D-QSAR model (q²=0.9132) demonstrated robust predictive accuracy, highlighting key structural attributes influencing biological activity. Synthetic schemes yielded three distinct series of indazole derivatives, which were subjected to bioassays for their anticancer, antioxidant and antimicrobial properties. Compounds 5b and 5'j exhibited noteworthy anticancer activity against A549 and MCF7 cell lines, surpassing certain existing drugs. Molecular dynamics simulations validated ligand stability, while Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profiling confirmed favorable pharmacokinetic attributes. Structure-Activity Relationship (SAR) analyses revealed that specific substitutions significantly enhanced biological efficacy. These findings underscore the therapeutic potential of indazole derivatives, prepare for further in vivo and clinical investigations.
Published Date: 2024-12-09; Received Date: 2024-11-06