2. Academic Validation
  3. Synthesis of piperazine-based benzimidazole derivatives as potent urease inhibitors and molecular docking studies

Synthesis of piperazine-based benzimidazole derivatives as potent urease inhibitors and molecular docking studies

  • Sci Rep. 2025 Aug 9;15(1):29220. doi: 10.1038/s41598-025-14723-4.
Delaram Shahriarynejad 1,  Navid Dastyafteh 2,  Fouzia Naz 3,  Meysam Talebi 1,  Sajedeh Safapoor 2,  Seyedeh Niloufar Ghafouri 4,  Homa Azizian 5,  Maryam Mohammadi-Khanaposhtani 6,  Bagher Larijani 2,  Mehdi Asadi 5,  Massoud Amanlou 7 8,  Mohammad Mahdavi 9,  Khalid Mohammed Khan 3 10
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 3 International Center for Chemical and Biological Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan.
  • 4 School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
  • 5 Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
  • 6 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 7 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. amanlou@tums.ac.ir.
  • 8 Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. amanlou@tums.ac.ir.
  • 9 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. momahdavi@tums.ac.ir.
  • 10 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
PMID: 40783587 DOI: 10.1038/s41598-025-14723-4
Abstract

The development of new bioactive compounds is important for progress in therapeutic research. In the present study, we describe the multistep synthetic approach to develop a library of novel benzimidazole analogs incorporating piperazine rings in order to increase their biological activity. In order to synthesize the desired benzimidazole analogs, the synthesis started with the easily accessible precursors between aniline and chloroacetyl chloride. It proceeded via a series of reactions, such as condensation, cyclization, and N-alkylation. TLC optimized each step, and spectroscopic methods such as CHN, IR, EIMS, 1H-NMR, and 13C-NMR were used to characterize the final products. The Urease inhibitory activity of the synthesized compounds was evaluated. It was discovered that almost all compounds were quite effective, even more potent (IC50 = 0.15-12.17 µM) than the standard thiourea (IC50 = 23.11 ± 0.21 µM). The structure-activity relationship (SAR) is also established, which displayed that compound 9 L (IC50 = 0.15 ± 0.09 µM) with -NO2 substitutions at meta position play a major role in Urease inhibition and figure out as the most potent analog of the library. These results were further verified by molecular docking analysis, which indicated favorable binding energies and interactions of the compounds with the Urease active site. This study not only depicts the importance of multistep synthesis but also the structure-based modification approach to produce new pharmacophores for therapeutic applications.

Keywords

Benzimidazole; Docking study; Piperazine; Urease inhibition.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z