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Selection Of Theaflavin 2B As a Potential HSP90 Antagonist Semi-rigid Ligand Docking Analysis

Akinsehinwa, S. A.; Medayedupin, O.

2022-06-28 pharmacology and toxicology
10.1101/2022.06.24.497557 bioRxiv
Show abstract

Heat shock protein 90 (HSP90) is an abundant molecular chaperone playing critical role as mediator of proper folding, maturation and stability of diverse client cellular proteins and has been reported to be overexpressed at a level of 2-10 folds relative to 1-2 folds of healthy cells. Geldanamycin and its derivatives (17AAG and 17 DMAG) has been developed to combat this but are known to be associated with primary side effects including plague, nausea, vomit, liver toxicity, hence the need to discover a relative safe and more potent inhibitor. The aim of this study is to determine the inhibitory potential of the Theaflavin 2B, a furanocoumarin derivative, which has been documented to have anti-tumour activity against human prostate carcinoma DU145 cells via computational techniques. To this effect, theaflavin 2B was retrieved from PubChem database, and screened against HSP90 for its inhibitory effect, which resulted in relatively higher binding affinity of -9.2Kcal/mol relative to that of the standard (-6.4 Kcal/mol). Computational docking analysis were performed using PyRx, AutoDock Vina option based on scoring functions and the target was validated so as to ensure that the right target and appropriate docking protocol was followed for this analysis. The docking studies of Theaflavin 2B with HSP90 showed that this ligand is a druggable molecule which docks well with HSP90 target. Therefore, theaflavin 2B molecule is a very good candidate for inhibiting HSP90 and presented it as good candidate for further evaluation as a potential therapeutic agent for cancer therapy.

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