SYNTHESIS AND MOLECULAR DOCKING STUDY OF BIS-THIOBARBITURATE DERIVATIVES AS EFFECTIVE INHIBITORS OF BETA-GLUCURONIDASE

Abstract

Bis-thiobarbiturate derivatives 1-15 have been synthesized and evaluated for their in vitro βglucuronidase inhibitory potential. The structures of all compounds were confirmed throughspectroscopic techniques such as EI-MS and HNMR. Compounds 13 IC50 = 29.42 ± 0.61µM showed potent β-glucuronidase inhibitory potential better than the standard inhibitor D-saccharicacid 1, 4 lactone, IC50 = 48.4 ± 1.25 µM . The compounds 2 IC± 0.22 µM , 4 IC50 = 55.12 ± 1.13µM and 9 IC50 = 49.84 ±1.46µM showed b-glucuronidaseinhibitory potential comparable to the standard inhibitor. Compounds 1 IC50 = 68.45 ± 0.33 µM , 5 IC50 = 61.18 ± 1.42µM , 6 IC50 = 92.57 ±2.80 µM , 7 IC50 = 61.27 ± 0.45 µM , 8 IC50 = 62.85 ±0.79µM , and 12 IC50 = 77.56 ± 1.32µM also showed good inhibitory potential. The remainingcompounds are found to be completely inactive. The structure-activity relationship was establishedfor these compounds. This study identified a novel class of β-glucuronidase inhibitors

Keywords

• Organic Synthesis,Molecular Docking Studies,Thiobarbituric Acid,β-glucuronidaseInhibition,Thiobarbiturate

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