Title:2-Indolinone Derivatives as Potent Urease Inhibitors
VOLUME: 15 ISSUE: 8
Author(s):Momin Khan*, Muhammad Yousaf, Abdul Wadood, Zahid Hussain, Muhammad Naeem, Khair Zaman, Sana Shah, Khalid Mohammed Khan and Shahnaz Perveen
Affiliation:Department of Chemistry, Abdul Wali Khan University, Mardan-23200, Department of Chemistry, Abdul Wali Khan University, Mardan-23200, Department of Biochemistry, Abdul Wali Khan University, Mardan-23200, Department of Chemistry, Abdul Wali Khan University, Mardan-23200, Department of Chemistry, Abdul Wali Khan University, Mardan-23200, Department of Chemistry, Abdul Wali Khan University, Mardan-23200, Department of Chemistry, Abdul Wali Khan University, Mardan-23200, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, PCSIR Laboratoires Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi-75280
Keywords:2-Indolinone, urease inhibitor, docking studies, aromatic aldehydes, urease protein, MOE.
Abstract:Background: 2-Indolinone is a bicycle, heterocyclic compound analogous of indole
skeleton containing a carbonyl group at 2-position of the 5-membered ring. Recently, different biological
evaluations of oxindole derivatives have been reported. A variety of compounds with oxindoles
moiety exhibit useful pharmaceutical properties like anti-inflammatory, anti-bacterial, anticancer,
anti-proliferative, anti-hypertensive, anti-HIV and anti-convulsant activities.
Methods: In the present study, fifteen 6-chloro-3-oxindole derivatives (1-15) were screened for
urease inhibitory activity. The binding mode of the synthesized compounds was studied by molecular
docking and found good results. 6-Chloro-3-oxindole derivatives 1-15 were synthesized from
6-chlorooxindole by refluxing with different aromatic aldehydes in ethanol in the presence of
piperidine in high yields. Docking was carry out of the ligands into HCV NS3/4A protein. The
software package MOE (Molecular Operating Environment) was used for docking.
Results: Our present study has shown that compound 6 (IC50 = 13.34 ± 1.75 µM), 2 (IC50 = 16.67 ±
1.73 µM), and 5 (IC50 = 17.85 ± 2.21 µM) were found to be the most potent urease inhibitors as
compared to the standard thiourea (IC50 = 21.1 ± 0.11 µM).
Conclusion: Our present study has shown that Compounds 6 (IC50 = 13.34 ± 1.75 µM), 2 (IC50 =
16.67 ± 1.73 µM), and 5 (IC50 = 17.85 ± 2.21 µM) were found to be the most potent urease inhibitors
as compared to the standard thiourea (IC50 = 21.1 ± 0.11 µM). These may serve as lead compounds
for better urease inhibitors after fine tuning in the structure and further studies in future.
