In Silico Study of Innovative Compounds Targeting Protein (Survivin): Understandings into Cancer Therapeutics

Background: Survivin, also known as Baculoviral Inhibitor of Apoptosis Repeat Containing 5 (BIRC5), is a key protein involved in cell division and the inhibition of apoptosis, making it an essential component of eukaryotic cell biology. Survivin is highly expressed across all human tumor lines and is significant in cancer due to its dual function in promoting cell proliferation and inhibiting apoptosis. Programmed cell death (PCD) is critical for mammalian development and disease regulation. The dysregulation of apoptosis leads to uncontrolled cell proliferation, which contributes to tumor progression and metastasis. Survivin interacts with caspases, predominantly inhibiting Caspase-3 and Caspase-7, thereby playing a key role in dysregulating apoptosis. Given its preferential expression in tumor cells and its decisive role in carcinogenesis and chemoresistance, Survivin emerges as an attractive target for cancer treatment.Methods: Compounds from the PubChem database were screened using molecular docking. Lead candidates were then evaluated for drug-likeness and ADMET properties, and the stability of the top compound-protein complex was analyzed using molecular dynamics simulations.Results: The current study highlights the therapeutic potential of novel compounds designed to inhibit Survivin in cancer therapy. This probability is illuminated through the use of innovative techniques such as computer-generated (virtual) screening and molecular docking. The lead compounds have also been filtered for their drug-likeness and ADMET potential.Conclusion: The stability of the designated compounds has been investigated in-depth through MD simulations. The results from this study suggest that the compound CID:155104111 (1-[2-(difluoromethoxy)ethyl]-2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazol-3-ium-4,9-dione) is a potential lead candidate for targeting the Survivin protein, showing promise when compared to the standard inhibitor, YM155.