In-Silico Analysis of Benzo-Selenadiazole Hybrids: Reactivity and Anticancer Potential Assessed Through DFT, Molecular Dynamics, Molecular Docking, and ADMET

Fighting cancer is challenging, but targeting apoptosis pathways offers hope. Caspases 3 and 7 cleave substrates, leading to key features like phosphatidylserine exposure, nuclear condensation, and DNA fragmentation, driving cancer cell death. This understanding aids in developing targeted therapies to selectively eliminate cancer cells. This study explores the synthesis, characterization, and in-silico analysis of carvone-isoxazoline-selenadiazole hybrids (11a–e) as potential anticancer agents. Advanced NMR techniques, including COSY, HSQC, and HMBC, confirmed the structural integrity of the benzo[1–3]selenadiazole core. Among the derivatives, 11c stood out with a low HOMO-LUMO energy gap of 3.2 eV, indicating high reactivity. MEPS analysis revealed biologically active sites at −0.85 and 1.2 eV, while biological evaluations demonstrated 11c’s ability to induce apoptosis via caspase-3 activation with an IC50 of 2.1 μM, similar to doxorubicin. Strong docking interactions with apoptosis-related proteins further support this. Mature caspases 3 and 7 cleave a broad set of substrates, ultimately leading to apoptotic features such as phosphatidylserine exposure, nuclear condensation, and DNA fragmentation. ADMET analysis revealed favorable pharmacokinetics, with a logP of 2.5, and low toxicity risks, with an LD₅₀ value of >1000 mg/kg. Structure-activity relationships highlighted selenium’s pivotal role in enhancing activity. With potent anticancer properties and a promising drug profile, 11c is a compelling candidate for further cancer therapy development.