2. Academic Validation
  3. Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives

Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives

  • J Enzyme Inhib Med Chem. 2023 Dec;38(1):2235089. doi: 10.1080/14756366.2023.2235089.
Deepak Shilkar 1,  Mohd Usman Mohd Siddique 2,  Silvia Bua 3,  Sabina Yasmin 1 4,  Mrunali Patil 2,  Ajay Kumar Timiri 1,  Claudiu T Supuran 3,  Venkatesan Jayaprakash 1
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, India.
  • 2 Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, India.
  • 3 Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, Italy.
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
PMID: 37439360 DOI: 10.1080/14756366.2023.2235089
Abstract

A series of phthalimide-capped benzene sulphonamides (1-22) reported by our group for dengue Protease inhibitory activity have been evaluated for their Carbonic Anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds 1, 3, 10, and 15 showed hCA I inhibition, whereas 1, 4, and 10 showed hCA II inhibition at nanomolar concentrations. Among these compounds, 1 displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.

Keywords

Carbonic anhydrase; molecular docking; molecular dynamics; phthalyl sulphamoyl derivatives.

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