STRUCTURE AFFINITY RELATIONSHIP AND CHARACTERIZATION OF BENZOPORPHYRINS AS POTENT INHIBITORS OF YAP ONCOPROTEIN THROUGH IN SILICO EXPERIMENTS
Keywords:
YAP oncoprotein, BenzoporphyrinsAbstract
Objective: Yes activated protein (YAP) is a transcriptional coactivator and corepressor that plays a pivotal role in cell proliferation. Amplification of the YAP gene and over expression of the YAP oncoprotein are reported in various human cancer cell lines. Hence inhibition of YAP by small molecular ligands would control cell proliferation.
Methods: Autodock 4.2 was used to dock the designed ligands to the active site of YAP oncoprotein. Structure affinity relationship was carried out for 70 benzoporphyrin derivatives (SAfiR). Based on the SAfiR data, 8 benzoporphyrin derivatives were designed.
Results: 8 compounds were found to potentially inhibit YAP. Verteporfin was taken as the standard with a binding energyof -6.84 kcal/Mol.The designed compounds were found to have binding energy in the range of -8.85 kcal/mol to -7.61 kcal/mol.
Conclusion: Based on the substituent effects and reported pleiotropic property of verteporfin, 8 novel porphyrin derivatives were identified with potent inhibitory effect towards the YAP oncoprotein. Further virtual and high throughput approaches could potent compounds that are specifically targeted towards the YAP peptide.
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Author Biographies
M. Vijey Aanandhi, Department of Pharmaceutical Chemistry School of Pharmaceutical sciences Vels University
Professor
Department of Pharmaceutical Chemistry
P. Samuel Gideon George, Department of Pharmacy Practice School of Pharmaceutical sciences Vels University
Department of Pharmacy Practice
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