Dihydropyrimidones: As novel class of β-glucuronidase inhibitors

• Published in: Bioorganic and Medicinal Chemistry
• Main Author: Ali F.; Khan K.M.; Salar U.; Iqbal S.; Taha M.; Ismail N.H.; Perveen S.; Wadood A.; Ghufran M.; Ali B.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978791280&doi=10.1016%2fj.bmc.2016.06.002&partnerID=40&md5=ef9bc031727d6ea9efb356f0399856e6

Dihydropyrimidones 1–37 were synthesized via a ‘one-pot’ three component reaction according to well-known Biginelli reaction by utilizing Cu(NO3)2·3H2O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC50 = 28.16 ± .056 μM), 9 (IC50 = 18.16 ± 0.41 μM), 10 (IC50 = 22.14 ± 0.43 μM), 13 (IC50 = 34.16 ± 0.65 μM), 14 (IC50 = 17.60 ± 0.35 μM), 15 (IC50 = 15.19 ± 0.30 μM), 16 (IC50 = 27.16 ± 0.48 μM), 17 (IC50 = 48.16 ± 1.06 μM), 22 (IC50 = 40.16 ± 0.85 μM), 23 (IC50 = 44.16 ± 0.86 μM), 24 (IC50 = 47.16 ± 0.92 μM), 25 (IC50 = 18.19 ± 0.34 μM), 26 (IC50 = 33.14 ± 0.68 μM), 27 (IC50 = 44.16 ± 0.94 μM), 28 (IC50 = 24.16 ± 0.50 μM), 29 (IC50 = 34.24 ± 0.47 μM), 31 (IC50 = 14.11 ± 0.21 μM) and 32 (IC50 = 9.38 ± 0.15 μM) found to be more potent than the standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Molecular docking study was conducted to establish the structure–activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as1H,13C NMR, EIMS and HREI-MS. © 2016 Elsevier Ltd