Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies

  • ACS Med Chem Lett. 2024 Sep 30;15(10):1749-1755. doi: 10.1021/acsmedchemlett.4c00341.
Chiara Baroni  1 ,  Ilaria D'Agostino  2  3  4 ,  Gioele Renzi  4 ,  Jaydeo T Kilbile  5 ,  Yasinalli Tamboli  6 ,  Marta Ferraroni  1 ,  Simone Carradori  3 ,  Clemente Capasso  7 ,  Fabrizio Carta  4 ,  Claudiu T Supuran  4
Affiliations
  • 1. Department of Chemistry "Ugo Schiff", University of Florence, 50019, Sesto Fiorentino, Florence, Italy.
  • 2. Department of Pharmacy, University of Pisa, 56126, Pisa, Italy.
  • 3. Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, 66100, Chieti, Italy.
  • 4. NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, 50019, Sesto Fiorentino, Florence, Italy.
  • 5. University Department of Basic and Applied Sciences (Chemistry), MGM University, Aurangabad-431003, Maharashtra, India.
  • 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 Biology, Agriculture and Food Sciences, National Research Council (CNR), Institute of Biosciences and Bioresources, 80131 Naples, Italy.
PMID: 39411526 DOI: 10.1021/acsmedchemlett.4c00341
Abstract

Lasamide is a synthetic precursor and a contaminant of the diuretic Furosemide manufacturing process and represents a highly valuable building block for fragment-based drug discovery approaches. We assessed the ability of Lasamide to inhibit in vitro the human-expressed Carbonic Anhydrases by means of the stopped-flow technique, and we assessed its binding modes within hCAs II and XII-mimic catalytic clefts by X-ray crystallography. Interestingly, an unprecedented crystal form for the hCA IX mimic H-tag is reported and discussed herein.

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