Molecular Docking of MCL-1 Protein with Various Inhibitors for Cancer Treatment Research Article
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Abstract
Myeloid cell leukemia-1 (MCL-1), belonging to Bcl-2 protein family, regulates apoptosis and is frequently overexpressed in cancer cells, making it a potential target for anti-cancer therapies. In this study, Insilico drug design is employed to screen ten FDA approved drugs with various therapeutic applications, followed by molecular docking of four promising compounds exhibiting good ADME properties and no carcinogenicity and mutagenicity, to identify potential MCL-1 inhibitors with improved efficacy, reduced resistance, and minimal toxicity. Our analysis revealed strong binding affinities of drugs, cyclobenzaprine hydrochloride (-9.3 kcal/mol), miconazole nitrate (-8.4 kcal/mol), donepezil hydrochloride (-8.1 kcal/mol) and dorzolamide (-5.3 kcal/mol) due to significant interactions with the key active site amino acid residues of MCL-1 protein, mainly "hotspot" residue Arg263A, interacting through hydrogen bond. These interactions, crucial for protein activity, suggest a potential novel mechanism for destabilizing and inhibiting MCL-1 activity. Subsequently, suggesting their promising possibility as an effective anti-tumor agent. Overall, our findings suggest these drugs as potential MCL-1 inhibitors for treating tumors, though further experimental validation is required.
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