Exploring 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide (5-NPIC) Derivatives as Anticancer Agents: Synthesis, Docking and Molecular Dynamics Insights

Abstract

The synthesis and characterization of a series of 5-nitro-[Formula: see text]-phenyl-3-(phenylamino)-1[Formula: see text]-indazole-1-carboxamide 5-NPIC derivatives (5a– 5v) have been reported as anticancer agents in this study. These derivatives were synthesized by reacting 3-chloro-5-nitro-[Formula: see text]-phenyl-1[Formula: see text]-indazole-1-carboxamide (4) with a variety of aniline derivatives in isopropanol. FT-IR, 1H-NMR, 13C-NMR and mass spectral methods were employed to confirm the structures of analogues (5a– 5v). The anticancer activity evaluation of compounds 5a– 5v revealed that 3-((3-methoxyphenyl) amino)-5-nitro-[Formula: see text]-phenyl-1[Formula: see text]-indazole-1-carboxamide (5j) exhibited good efficacy. The stability of ligand–protein complexes was systematically evaluated using molecular dynamics simulations (MDS), which demonstrated a consistent and robust binding of the most potent compound within the binding sites of target proteins. The results confirmed the anticancer activity, which was further substantiated by comprehensive molecular docking analyses that revealed complex interactions involving hydrophobic contacts, electrostatic forces and hydrogen bonds. Our results would collectively provide invaluable insights into the intricate molecular structure and dynamics of receptor target sites, thereby establishing a solid foundation for the development of novel and potent anticancer agents with optimistic pharmaceutical implications in near future.