With an aim to develop novel potential antitumor agents, two series of benzene- and benzothiazole-sulfonamide derivatives, acting as effective human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors, have been developed using the tail approach. The synthesized compounds (XS-1 to XS-22) were assayed for the inhibition of physiologically relevant isoforms of hCA, the cytosolic CA I and II, the membrane-bound CA IV and tumor-associated CA IX. It was found the compounds of both series displayed low to medium nanomolar range inhibition against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular docking studies were carried out to explain those structural requirements that were liable for the discrimination among selected human carbonic anhydrase isoforms.

Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX

Zara S.;Carradori S.;
2022-01-01

Abstract

With an aim to develop novel potential antitumor agents, two series of benzene- and benzothiazole-sulfonamide derivatives, acting as effective human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors, have been developed using the tail approach. The synthesized compounds (XS-1 to XS-22) were assayed for the inhibition of physiologically relevant isoforms of hCA, the cytosolic CA I and II, the membrane-bound CA IV and tumor-associated CA IX. It was found the compounds of both series displayed low to medium nanomolar range inhibition against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular docking studies were carried out to explain those structural requirements that were liable for the discrimination among selected human carbonic anhydrase isoforms.
File in questo prodotto:
File Dimensione Formato  
EJMC 2022.pdf

Solo gestori archivio

Tipologia: PDF editoriale
Dimensione 6.73 MB
Formato Adobe PDF
6.73 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS 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/11564/790492
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 10
social impact