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ORIGINAL RESEARCH article

Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 12 - 2024 | doi: 10.3389/fchem.2024.1423385

Pyridylpiperazine based carbodithioates as Urease Inhibitors: Synthesis and biological evaluation

Provisionally accepted
Muhammad Akash Muhammad Akash 1Nehal Rana Nehal Rana 2Sana Aslam Sana Aslam 3Matloob Ahmad Matloob Ahmad 1*Muhammad J. Saif Muhammad J. Saif 1Aneeza Asghar Aneeza Asghar 2Sadia Sultan Sadia Sultan 4Sami Al HUSSAIN Sami Al HUSSAIN 5Afifa Liaqat Afifa Liaqat 2Sumera Zaib Sumera Zaib 2Magdi E. Zaki Magdi E. Zaki 5
  • 1 Government College University, Faisalabad, Faisalabad, Pakistan
  • 2 University of Central Punjab, Lahore, Punjab, Pakistan
  • 3 Department of Chemistry, Government College Women University, Faisalabad, Punjab, Pakistan
  • 4 Universiti Teknologi MARA Puncak Alam, Selangor, Selangor, Malaysia
  • 5 Imam Muhammad ibn Saud Islamic University, Riyadh, Saudi Arabia

The final, formatted version of the article will be published soon.

    Urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacteria because of its pivotal role in aiding the bacterium's colonization and growth within the gastric mucosa. In order to control the harmful consequences of bacterial infections, the urease inhibition presents itself as a promising and effective approach. The current research designed to synthesize pyridylpiperazine based carbodithioate derivatives 5a-5n and 7a-7n that could serve as potential drug candidates for preventing bacterial infections through the urease inhibition. The synthesized carbodithioate derivatives 5a-5n and 7a-7n were explored to assess their ability to inhibit the urease enzyme, after their structural explication by gas chromatography mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity in comparison to the reference drug. Among the compounds tested, 5j (bearing o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC50 value of 5.16 ± 2.68 μM. This IC50 value is notably lower than that of thiourea (23 ± 0.03 μM), indicating a significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified.

    Keywords: Pyridine and piperazine derivatives, Heterocyclic carbodithioates, Urease inhibitors, molecular docking, synthesis and biological evaluation

    Received: 25 Apr 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Akash, Rana, Aslam, Ahmad, Saif, Asghar, Sultan, Al HUSSAIN, Liaqat, Zaib and Zaki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Matloob Ahmad, Government College University, Faisalabad, Faisalabad, Pakistan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.