Synthesis of new urease enzyme inhibitors as antiulcer drug and computational study

• Published in: Journal of Biomolecular Structure and Dynamics
• Main Author: Taha M.; Ismail S.; Imran S.; Almandil N.B.; Alomari M.; Rahim F.; Uddin N.; Hayat S.; Zaman K.; Ibrahim M.; Alghanem B.; Islam I.; Farooq R.K.; Boudjelal M.; Khan K.M.
• Format: Article
• Language: English
• Published: Taylor and Francis Ltd. 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85104566360&doi=10.1080%2f07391102.2021.1910072&partnerID=40&md5=a1a8b56d06c008f8f5c02429c5d4bf9a

In search of potent urease inhibitor indole analogues (1–22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1–22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.