A series of new 3- and 7-substituted sulfocoumarins was obtained by several cyclization reactions and subsequent derivatization for screening as prodrug inhibitors of the human (h) cancer-associated carbonic anhydrases (CAs) IX and XII. All products were ineffective inhibitors against the off-target hCA I and II, whilst hCAs IX and XII were inhibited with inhibition constants (KIs) spanning from low nanomolar to the high micromolar range, according to the sulfocoumarin derivatization pattern. In particular, sulfocoumarin 15 turned out to be the most potent and selective inhibitor herein reported (hCA I and II: KI > 100 µM; hCA IX: KI = 22.9 nM; hCA XII: KI = 19.2 nM). Considering that hCA IX and XII validated anti-tumor targets, such prodrug, isoform-selective inhibitors as the sulfocoumarins reported here may be useful for identifying suitable drug candidates for clinical trials.

Continued Structural Exploration of Sulfocoumarin as Selective Inhibitor of Tumor-Associated Human Carbonic Anhydrases IX and XII / Giovannuzzi, Simone; Capasso, Clemente; Nocentini, Alessio; Supuran, Claudiu T. - In: MOLECULES. - ISSN 1420-3049. - ELETTRONICO. - 27:(2022), pp. 4076-4076. [10.3390/molecules27134076]

Continued Structural Exploration of Sulfocoumarin as Selective Inhibitor of Tumor-Associated Human Carbonic Anhydrases IX and XII

Giovannuzzi, Simone;Nocentini, Alessio
;
Supuran, Claudiu T
2022

Abstract

A series of new 3- and 7-substituted sulfocoumarins was obtained by several cyclization reactions and subsequent derivatization for screening as prodrug inhibitors of the human (h) cancer-associated carbonic anhydrases (CAs) IX and XII. All products were ineffective inhibitors against the off-target hCA I and II, whilst hCAs IX and XII were inhibited with inhibition constants (KIs) spanning from low nanomolar to the high micromolar range, according to the sulfocoumarin derivatization pattern. In particular, sulfocoumarin 15 turned out to be the most potent and selective inhibitor herein reported (hCA I and II: KI > 100 µM; hCA IX: KI = 22.9 nM; hCA XII: KI = 19.2 nM). Considering that hCA IX and XII validated anti-tumor targets, such prodrug, isoform-selective inhibitors as the sulfocoumarins reported here may be useful for identifying suitable drug candidates for clinical trials.
27
4076
4076
Giovannuzzi, Simone; Capasso, Clemente; Nocentini, Alessio; Supuran, Claudiu T
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1289756
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact