Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents.
A series of 25 compounds, some of which previously were described as inhibitors of human liver microsomal oxidosqualene cyclase (OSC), were tested as inhibitors of Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana OSCs expressed in an OSC-defective strain of S. cerevisiae. The screening identified three derivatives particularly promising for the development of novel anti-Trypanosoma agents and eight derivatives for the development of novel anti-Pneumocystis agents.
Balliano
Gianni
G
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, via P. Giuria 9, 10125 Torino, Italy. gianni.balliano@unito.it
Dehmlow
Henrietta
H
Oliaro-Bosso
Simonetta
S
Scaldaferri
Matilde
M
Taramino
Silvia
S
Viola
Franca
F
Caron
Giulia
G
Aebi
Johannes
J
Ackermann
Jean
J
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017360:Arabidopsis / Q000201:enzymology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002855:Chromatography, Thin Layer; D015195:Drug Design; D006801:Humans; D019751:Intramolecular Transferases / Q000737:chemistry* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D045363:Pneumocystis carinii / Q000201:enzymology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013261:Sterols / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000201:enzymology*
D000977:Antiparasitic Agents; D013261:Sterols; D019751:Intramolecular Transferases; C021924:lanosterol synthase