An α-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this α-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease.
Inhibition of carbonic anhydrase from Trypanosoma cruzi for the management of Chagas disease: An underexplored therapeutic opportunity / Supuran, Claudiu T. - In: FUTURE MEDICINAL CHEMISTRY. - ISSN 1756-8919. - ELETTRONICO. - 8:(2016), pp. 311-324. [10.4155/fmc.15.185]
Inhibition of carbonic anhydrase from Trypanosoma cruzi for the management of Chagas disease: An underexplored therapeutic opportunity
SUPURAN, CLAUDIU TRANDAFIR
2016
Abstract
An α-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this α-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.