Vernekar, Beena K.Harmalkar, Nikita N.Gaonkar, Sanket K.Barretto, Delicia A.Maliwal, DeepikaPissurlenkar, Raghuvir R.Bhowmik, Pradip K.Dhuri, Sunder N.2025-02-172025-02-172025Journal of Molecular Structure Volume. 1332; 2025; 141694 pp.0022-2860https://doi.org/10.1016/j.molstruc.2025.141694http://khandolacollege.ndl.gov.in/handle/123456789/146Two bioactive nickel(II) compounds of mefenamic acid (Hmef) with substituted α-diimines as co-ligands have been characterised using various spectroscopic methods and evaluated for cytotoxicity, DNA interaction and antioxidant studies, molecular docking and dynamics studies. Single crystal structures of [Ni(Mef-O)2(etobpy)(H2O)] 1 and [Ni(Mef-O)2(dmbpy)(H2O)(DMF)] 2, (etobpy = 4,4′-diethoxy 2,2′-bipyridine, dbmbpy = 4,4′-dimethyl-2,2′-bipyridine and DMF = N, N′-dimethylformamide) have been determined using single crystal X-ray diffraction technique. The mefenamato ligand adopts two types of coordination modes (mono- and bidentate) in 1, while in compound 2 both mef ligands display monodentate behaviour. The Ni(II) ion in both compounds shows a distorted octahedral geometry binding to two N and four O atoms. The cytotoxicity results revealed the activity of 1 and 2 against cancerous HepG2 in a dose-dependent manner. % DPPH free radical scavenging activity of 1 and 2 when performed, they exhibited IC50 values of 17.02±0.85 μM and 19.89±0.73 μM respectively, depicting their antioxidant nature. DNA binding properties of 1 and 2 were assessed by UV absorption spectroscopy, which suggested an intercalating binding between the complexes and the DNA. Both complexes act as potential agents towards DNA cleavage with the dose-dependent rise of Form II and III DNA. Further, Their interactions with DNA were studied using molecular docking and molecular dynamics simulations. Both 1 and 2 are intercalating in the major groove of DNA fragment, destabilizing the double helix strand during simulation, proving as potential candidates for cytotoxicity.enNATURAL SCIENCES::ChemistryArticle