A series of novel sulfonamide derivatives bearing pyrrole and pyrrolopyrimidine scaffolds were synthesized and screened as carbonic anhydrase inhibitors. The inhibition activity of the synthesized compounds was evaluated against the cytosolic human carbonic anhydrase isoforms I and II and the transmembranal isoforms IX and XII. Several candidates showed potent inhibitory activity against IX and XII isoforms. Furthermore, ex vivo screening of cytotoxic selectivity and activity of the most potent derivatives were carried out against normal cells (WI38) and cervical cancer cell line (HeLa) under normal and hypoxic conditions using acetazolamide as reference drug. Compound 11b potency was nearly three folds higher in hypoxic than normoxic condition whereas that of compound 11f was nearly four folds higher in hypoxic vs. normoxic HeLa cells. All the screened derivatives exhibited less potency on normal cells (WI38). Molecular docking was carried out to discover the possible binding mode of compounds within the active site of isoform CA IX. (C) 2019 Elsevier Masson SAS. All rights reserved.

Pyrrolo and pyrrolopyrimidine sulfonamides act as cytotoxic agents in hypoxia via inhibition of transmembrane carbonic anhydrases / Khalil, Omneya M; Kamal, Aliaa M; Bua, Silvia; El Sayed Teba, Heba; Nissan, Yassin M; Supuran, Claudiu T. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - ELETTRONICO. - 188:(2020), pp. 0-0. [10.1016/j.ejmech.2019.112021]

Pyrrolo and pyrrolopyrimidine sulfonamides act as cytotoxic agents in hypoxia via inhibition of transmembrane carbonic anhydrases

Bua, Silvia;Supuran, Claudiu T
2020

Abstract

A series of novel sulfonamide derivatives bearing pyrrole and pyrrolopyrimidine scaffolds were synthesized and screened as carbonic anhydrase inhibitors. The inhibition activity of the synthesized compounds was evaluated against the cytosolic human carbonic anhydrase isoforms I and II and the transmembranal isoforms IX and XII. Several candidates showed potent inhibitory activity against IX and XII isoforms. Furthermore, ex vivo screening of cytotoxic selectivity and activity of the most potent derivatives were carried out against normal cells (WI38) and cervical cancer cell line (HeLa) under normal and hypoxic conditions using acetazolamide as reference drug. Compound 11b potency was nearly three folds higher in hypoxic than normoxic condition whereas that of compound 11f was nearly four folds higher in hypoxic vs. normoxic HeLa cells. All the screened derivatives exhibited less potency on normal cells (WI38). Molecular docking was carried out to discover the possible binding mode of compounds within the active site of isoform CA IX. (C) 2019 Elsevier Masson SAS. All rights reserved.
2020
188
0
0
Khalil, Omneya M; Kamal, Aliaa M; Bua, Silvia; El Sayed Teba, Heba; Nissan, Yassin M; 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 identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1308061
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 22
social impact