In silico study of new carbonic anhydrase inhibitor derivatives bearing 1, 3, 4-Oxadiazole moiety with promising anti-cancer activity.

Abstract

Objectives: Molecular docking simulations were performed to assess the theoretical binding affinities of six (6) compounds created where they are derivatives having 1,3,4, oxadiazole moiety, and their target was cancer and Human carbonic anhydrase IX (PDB code: 6U4T). Using ChemDraw Ultra 12.0, the molecular structure was meticulously sketched. Molecular Operating environment software was used to verify the developed compounds by looking at their S. score and Rmsd values. Promising activity was seen with these proteins from the theoretically generated compounds, which exhibited strong binding contacts with the receptor active pocket.   Methods: Chemically by joining together several oxadiazole derivatives, sulfanilamide analogues (IVa-IVd) may be created in the lab. Molecular docking and ligand/receptor priming by MOE software. Results: Acetazolamide was selected because it had the same pharmacophore as the sulfanilamide group, and cisplatin was used in clinical trials for cancer therapy. IVc and IVa yielded max score and irrevocable relationship compared with acetazolamide and cisplatin. Conclusion: The MOE docking results validated the potent anticancer activity, the identified compounds showing good binding affinity with target proteins relative to the reference drugs (Acetazolamide and cisplatin). The most effective anticancer compounds were IVc and IVa, which yielded a maximum score with a Rmsd of less than 2, the MOE docking results were able prove this. Compounds IVc and IVa exhibited the greatest cytotoxic impact of the synthetic compounds against MCF7, and all four synthesized compounds showed a superior safety profile than the standards in MCF10a.