A series of isothiazole dioxides was synthesized and evaluated as inhibitors of protein farnesyltransferase from the parasite that causes African sleeping sickness (Trypanosoma brucei). The most potent compound in the series inhibited the parasite enzyme with an IC50 of 2 μM and blocked the growth of the bloodstream parasite in vitro with an ED50 of 10 μM. The same compound inhibited rat protein farnesyltransferase and protein geranylgeranyltransferase type I only at much higher concentration. © 2002 Elsevier Science Ltd. All rights reserved.
Isothiazole dioxides: Synthesis and inhibition of Trypanosoma brucei protein farnesyltransferase / F. Clerici, M.L. Gelmi, K. Yokoyama, D. Pocar, W.C. Van Voorhis, F.S. Buckner, M.H. Gelb. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 12:16(2002), pp. 2217-2220. [10.1016/S0960-894X(02)00338-4]
Isothiazole dioxides: Synthesis and inhibition of Trypanosoma brucei protein farnesyltransferase
F. ClericiPrimo
;M.L. GelmiSecondo
;D. Pocar;
2002
Abstract
A series of isothiazole dioxides was synthesized and evaluated as inhibitors of protein farnesyltransferase from the parasite that causes African sleeping sickness (Trypanosoma brucei). The most potent compound in the series inhibited the parasite enzyme with an IC50 of 2 μM and blocked the growth of the bloodstream parasite in vitro with an ED50 of 10 μM. The same compound inhibited rat protein farnesyltransferase and protein geranylgeranyltransferase type I only at much higher concentration. © 2002 Elsevier Science Ltd. All rights reserved.
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
