Screening of Anti-Cancer Properties of Beta-Sitosterol and its Derivatives against Microtubules: Molecular Modeling Approach‎

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A phytosterol compound, beta-sitosterol is found in abundance in many plants, fruits, and vegetables. They possess numerous health benefits and clinical uses including medicinal properties such as anti-diabetic, anti-atherogenic, anti-asthmatic, etc. The compound was also reported to possess anti-cancer property against various cancer cell lines. Microtubules which are hollow fibrous shafts and made up of tubulin protein play essential roles in cell division, cell movement and intracellular transport. Due to their major role in cell division, microtubules are considered as an attractive target for designing potent anti-cancer agents. Given their importance, the present study describes the molecular docking of beta-sitosterol and its analogs with the alpha/beta form of tubulin. For this, small molecule compounds structurally similar to beta-sitosterol were retrieved from PubChem and Binding databases. In the subsequent step, High Throughput Virtual screening was carried out with the tubulin-colchicine complex. Based on the virtual screening results and the nature of active site residues of the protein complex, the screened compounds were further taken to Induced Fit Docking studies using Schrodinger’s GLIDE. Hydrogen bond interactions were analyzed between the compounds and active site amino acid residues. QikProp module and FAF-Drugs tools were used to analyze the pharmacokinetic properties of the selected compounds. Among the tested compounds, few compounds were found to satisfy all the in silico parameters and can be developed as potent inhibitors targeting microtubules.