IN SILICO SCREENING OF HESPERETIN AND NARINGENIN ESTER DERIVATIVES AS ANTICANCER AGAINST P-GLYCOPROTEIN
Objective: Study the in silico P-Glycoprotein (P-GP) inhibition activity of hesperetin and naringenin ester derivatives. Acyl group substituent was different in the length of the carbon atom chain (acetyl, propionyl, butyryl and valeryl).
Methods: Partition coefficient was predicted by the Chem Draw Ultra program. In silico docking using PLANTS program and visualized by Yasara program. The model of three dimension enzyme structures used in this research was P-Glycoprotein (P-GP) binding pocket with the Protein Data Bank (PDB) code 1MV5. Two dimensions and three dimension conformation models of hesperetin and naringenin ester derivatives and verapamil as the standard P-GP inhibitor generated by using the Marvin Sketch program.
Results: Hesperetin and naringenin have a lower partition coefficient than verapamil. It means that their solubility in the oil phase to cross the cell membrane was lower than verapamil. Trivaleryl hesperetin and trivaleryl naringenin have a higher partition coefficient than verapamil. It means that their solubility in the oil phase to cross the cell membrane was higher than verapamil. Docking score of hesperetin and naringenin as the lead compound was higher than verapamil as the P-GP inhibitor standard compound. It means that hesperetin and naringenin have a weaker interaction to target protein than verapamil. Ester derivatives of hesperetin and naringenin with the increasing the length of the acyl carbon atom chain substituted on hesperetin and naringenin will increase the P-GP inhibition activity. Butyryl and valeryl substituted as the acyl substituent to the hesperetin and naringenin shows the lower docking score than verapamil as the P-GP inhibitor standard compound. It means that butyryl and valeryl substituted as the acyl substituent to the hesperetin and naringenin have a stronger interaction to target protein than verapamil.
Conclusion: Increasing of the length of the acyl carbon atom chain substituted on hesperetin and naringenin it will increase the P-Glycoprotein (P-GP) inhibition activity. Trivaleryl hesperetin has the best activity in this study and thus to be a good compound to be synthesized and to be combined with anticancer drug.
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