Synthesis of novel disulfide and sulfone hybrid scaffolds as potent β-glucuronidase inhibitor

• Published in: Bioorganic Chemistry
• Main Author: Taha M.; Ismail N.H.; Imran S.; Wadood A.; Rahim F.; Al Muqarrabin L.M.R.; Zaki H.M.; Ahmat N.; Nasir A.; Khan F.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978792041&doi=10.1016%2fj.bioorg.2016.07.002&partnerID=40&md5=fab601fd5abd5eb3632e5e695647f875

Novel series of disulfide and sulfone hybrid analogs (1 −2 0) were synthesized and characterized through EI-MS and 1H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20–88.16 μM as compared to standard D-saccharic acid 1,4 lactone (48.4 ± 1.25 μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies. © 2016 Elsevier Inc.