Molecular Docking and Admet Studies of Cholesta-22, 24-Dien-5-Ol, 4, 4-Dimethyl Compound for the Antibacterial Property

Abstract

Objective: Bacterial infections are posing a serious threat to the human health because of their high frequency and rapid transmission. Staphylococcus aureus is a Gram-positive bacterium responsible for a wide range of clinical infections. Treating these infections presents a significant challenge in modern medicine, primarily due to the rise of drug-resistant strains. Cholesta-22,24-dien-5-ol, 4,4-dimethyl, a steroidal compound found in various plant, fungal, and animal species, has shown notable biological activities, including antibacterial and trypanocidal effects. The primary goal of this study is to evaluate the binding affinity of Cholesta-22,24-dien-5-ol, 4,4-dimethyl against seven distinct target proteins of Staphylococcus aureus, using norfloxacin as a reference drug, and to assess the ADMET properties of the compound.

Methods And Materials: The binding affinity between the ligand and protein was determined using rigid docking with AutoDock Vina 1.5.6. The 3D structures of seven antibacterial target proteins were obtained from the Protein Data Bank. The ligand molecules were generated using ChemDraw Professional. Rigid docking was applied to calculate the binding affinities between the ligand and the proteins.

Results:  The binding affinity of Cholesta-22,24-dien-5-ol, 4,4-dimethyl compound with seven different target proteins of staphylococcus aureus that is dihydrofolate reductase (PDB ID:2W9S), DNA gyrase (PDB ID: 3U2D), dehydrosqualene synthase (PDB ID:2ZCO), clumping factor A(PDB ID:1N67),fibrinogen binding protein (PDB ID:3DOA), pantothenate synthase (PDB ID: 2X3F),Staphylococcus aureus sortase A (PDB ID:1T2P) were studied using molecular docking tool Auto dock vina 1.5.6 and the docking scores were -9.0,-8.1,-8.6, -9.1,-7.8,-7.3,and -7.3 respectively. 2D interactions were visualized using Biovia discovery studio 2021. ADMET properties were studied using the web tool Swiss ADME.

Conclusion: In summary, Cholesta-22,24-dien-5-ol, 4,4-dimethyl compound exhibits promising results based on the in-silico studies in comparison with the reference drug norfloxacin. The docking studies of the compound with the protein dihydrofolate reductase (PDB ID:2W9S) and clumping factor A (PDB ID:1N67) have shown the highest docking score of -9.0 and -9.1 respectively. ADMET studies of the compound were also reported.