Photoinduced electron transfer photodecomposition of 1, 4-Dihydropyridine derivative phototoxic drug Manidipine, Docking and Molecular Dynamic studies

Abstract The present investigation focuses on the photochemical transformation of Manidipine (1) using ultraviolet-A light while being accompanied by an electron-donating agent (Et3N) and an electron-accepting component (CCl4). This resulted in the formation of photoproducts, identified as 2-[4-(diphenylmethyl) piperazin-1-yl] ethyl methyl2,6-dimethyl-4-(3-amino-phenyl)-1,4 dihydropyridine-3,5-dicarboxylate (2) and 2- [4-(diphenyl methyl) piperazin-1-yl] ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)- pyridine-3,5-dicarboxylate (3) from its spectral properties (IR, NMR and Mass spectra). The formation of photoproducts was rationalized by invoking a mechanism driven by photoinduced electron transfer. In addition, the binding affinities through docking and molecular dynamics studies were performed on parent drug and their photoproduct against tyrosinase enzyme for their correlation with phototoxic effect. The outcomes imply that all the compounds effectively occupied the enzymes’ active site, displaying substantial binding energies. These results were confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with the radius of gyration (Rg) and solvent accessible surface area (SASA) that indicated a stable and compact state throughout the simulation time. This data suggests that drug users should restrict exposure to radiation (natural or artificial) to avoid drug-induced phototoxic effects.