Abstract:
Two bioactive nickel(II) compounds of mefenamic acid (Hmef) with substituted Aplha-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) sub(2)(etobpy)(H sub(2)O)] 1 and [Ni(Mef-O) sub(2)(dmbpy)(H sub(2)O)(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. Percent DPPH free radical scavenging activity of 1 and 2 when performed, they exhibited IC sub(50) values of 17.02 plus-minus 0.85 Mu M and 19.89 plus-minus 0.73 Mu M 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.
