Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Sulfonamide-Phosphonate Hybrids As New Carbonic Anhydrase Inhibitors: In Vitro Enzymatic Inhibition, Molecular Modeling, and Admet Prediction Publisher



Zareei S1 ; Mohammadikhanaposhtani M2 ; Adib M1 ; Mahdavi M3 ; Taslimi P4, 5
Authors
Show Affiliations
Authors Affiliations
  1. 1. School of Chemistry, Alborz Campus, University of Tehran, Tehran, 14155-6619, Iran
  2. 2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, 74100, Turkey
  5. 5. Department of Chemistry, Faculty of Science, Istinye University, Istanbul, Turkey

Source: Journal of Molecular Structure Published:2023


Abstract

In the presented work, we report the synthesis of a new series of sulfonamide-phosphonate hybrids 4a-m. These newly synthesized compounds were assessed for their inhibitory effects toward two human carbonic anhydrase isoforms I and II (hCA I and II). These examined isoforms were as well inhibited by the most of prepared sulfonamide-phosphonates in comparison to standard inhibitor acetazolamide. Obtained data exhibited that compounds 4b-m with Ki values in the range of 8.11–48.08 nM were more potent than standard drug acetazolamide with Ki value of 64.52 Nm against hCA I. Moreover, all the synthesized compounds (Ki values = 7.08–64.24 nM), with the exception of compound 4b, were more potent than acetazolamide (Ki value = 75.36) against hCA II. In particular, sulfonamide-phosphonates 4l and 4j, respectively, with substituents 5‑chloro-2-nitro and 2,3-dichloro emerged as the most potent hCA inhibitors. Thereafter, the molecular docking of compounds 4l and 4j at hCA I and II active sites was performed and the obtained results revealed that these compounds interacted whit the important amino acids of the active site. Finally, the predicted parameters of Lipinski's rule of five, ADME, and toxicity analysis showed that compounds 4l and 4j had good drug-likeness and acceptable physicochemical properties. Therefore, the hybridization of the sulfonamide and phosphonate moieties could be promising strategy for achieve to potent lead compounds for inhibition of hCA. © 2022 Elsevier B.V.