Abstract
Survivin (IAP proteins) remains an important target for anticancer drug development as it is reported to be over-expressed in tumor cells to enhance resistance to apoptotic stimuli. The study focuses on virtual screening of marine compounds inhibiting survivin, a multifunctional protein, using a computational approach. Structures of compounds were prepared using ChemDraw Ultra 10. Software and converted into its 3D PDB structure and its energy was minimized using Discovery Studio client 2.5. The target protein, survivin was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling was carried out on marine compounds and the filtered compounds were further promoted for molecular docking analysis and interaction studies using AutoDock Tools 4.0. Molecular docking results revealed that analog (AP 4) of Aplysin, showed very promising inhibitory potential against survivin with a binding energy of -8.75 kcal/mol and Ki 388.28 nM as compared to its known inhibitor, Celecoxib having binding energy of -6.65 kcal/mol and Ki 13.43 μM. AP 4. The analog depicted similarity in pattern when compared to standard. The result proposes AP 4, is an effective molecule exhibiting prominent potential to inhibit survivin and thus promoting apoptosis in tumor cells.
Highlights
Survivin (IAP proteins) remains an important target for anticancer drug development as it is reported to be over-expressed in tumor cells to enhance resistance to apoptotic stimuli
It was accounted that survivin augmented levels of diverse members of the inhibitor of apoptosis (IAP) family have restrains cell death persuaded via the extrinsic and intrinsic been reported in many cancer types [3] and over-expression of apoptotic pathways and bestows resistance to apoptosis by IAP proteins has been reported to enhance resistance to apoptotic directly repressing caspase activity
B X-interacting protein (HBXIP) complex bound to pro-caspase-9, Survivin (BIRC5) being an averting the recruitment of apoptotic protease activating important member of the inhibitor of apoptosis (IAP) family is factor 1 (Apaf-1) to the apoptosome [10]
Summary
Survivin (IAP proteins) remains an important target for anticancer drug development as it is reported to be over-expressed in tumor cells to enhance resistance to apoptotic stimuli. Survivin is well reported to be responsible for Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the up-regulating vascular endothelial growth factor (VEGF) and only FDA (Food and Drug Administration) approved drug for inducing angiogenesis in tumors by accumulating β-catenin in the treatment of FAP (Familial adenomatous polyposis) patients the cytoplasm and inducing its translocation to the nucleus to that is known to induce apoptosis and suppressed the survivin form β-catenin/T-cell factor (TCF) transcriptional activator expression in HCT-116 cells [17]. The study has been turn phosphorylates survivin allowing it to form complex with carried out successfully to predict the role of marine compound
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