2. Academic Validation
  3. Novel 2,4-Dichloro-5-sulfamoylbenzoic Acid Oxime Esters: First Studies as Potential Human Carbonic Anhydrase Inhibitors

Novel 2,4-Dichloro-5-sulfamoylbenzoic Acid Oxime Esters: First Studies as Potential Human Carbonic Anhydrase Inhibitors

  • ACS Med Chem Lett. 2024 May 23;15(6):972-978. doi: 10.1021/acsmedchemlett.4c00206.
Jaydeo T Kilbile 1,  Suryakant B Sapkal 1,  Gioele Renzi 2,  Ilaria D'Agostino 2 3,  Luigi Cutarella 4,  Mattia Mori 4,  Barbara De Filippis 5,  Imadul Islam 6,  Maria Luisa Massardi 7,  Elena Somenza 7,  Roberto Ronca 7,  Yasinalli Tamboli 6,  Fabrizio Carta 2,  Claudiu T Supuran 2
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Basic and Applied Sciences, MGM University, Chhatrapati Sambhajinagar, 431003 Maharashtra, India.
  • 2 NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Sesto Fiorentino, 50019 Florence, Italy.
  • 3 Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
  • 4 Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
  • 5 Department of Pharmacy "G. d'Annunzio", University of Chieti-Pescara, 66100 Chieti, Italy.
  • 6 King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh 14811, Saudi Arabia.
  • 7 Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
PMID: 38894925 DOI: 10.1021/acsmedchemlett.4c00206
Abstract

In this study, a focused library of oxime ester derivatives of 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff Bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I and II, as well as the transmembrane and tumor-associated IX and XII isoforms. As a result, we obtained a first line of knowledge on lasamide derivatives potentially useful for development as CA inhibitors (CAIs). In particular, we focused our attention on the derivative 11, which was selective toward hCAs IX and XII over the cytosolic isoenzymes. An in silico study was conducted to assess the binding mode of 11 within hCAs IX and XII. Also, antiproliferative assays highlighted promising derivatives. The data obtained in this study are currently in use for the development of better-performing compounds on the tumor-associated isoforms.

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