Exploring tricycle acridines as prospective urease inhibitors: synthesis via microwave assistance, in vitro evaluation, kinetic profiling, and molecular docking investigations.

Manzoor, Mehwish; Solangi, Mehwish; Perveen, Shahnaz; Salar, Uzma; Naz, Fouzia; Iqbal, Jamshed; Hussain, Zahid; Imran, Aqeel; Taha, Muhammad; Khan, Khalid Mohammed

The current research deals with the microwave-assisted green synthesis of two acridine-based libraries and in vitro urease inhibitory activities. The first library is based on 9-phenyl acridine 1–13 derivatives, while the second is based on 10H-acridin-9-one 14–33 derivatives. All compounds were characterized using FTIR, EI-MS, 1H-NMR, and CHNX techniques. As a result of in vitro evaluation of the synthesized derivatives, most compounds showed potent inhibitory activity against urease with IC50 values ranging from 0.91 to 11.84 µM. Thiourea was used as the standard (IC50 = 19.43 ± 0.18 µM). The structure–activity relationship (SAR) was established to identify key relationships between studied compounds' chemical structure and biological activity. The kinetic studies revealed a competitive mode of inhibition by the compounds. In addition, molecular docking and MD simulation studies were conducted to determine the different interactions between the ligands (compounds) and the enzyme's active site for the retention time of the ligand into the active pocket of the protein. Thus, it is well-known that inhibiting the urease enzyme activity effectively treats infections caused by Helicobacter pylori. This study has identified that these synthetic acridines may serve as promising lead candidates as urease inhibitors.

MOLECULAR docking; ACRIDINE derivatives; UREASE; ACRIDINES; BINDING sites; HELICOBACTER pylori infections

Journal of the Iranian Chemical Society, 2024, Vol 21, Issue 4, p1163

1735-207X

Academic Journal

10.1007/s13738-024-02990-3