Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase.
Studies on the mode of action of a series of bisphosphonates derived from fatty acids, which had previously proved to be potent inhibitors against Trypanosoma cruzi proliferation in in vitro assays, have been performed. Some of these drugs proved to be potent inhibitors against the intracellular form of the parasite, exhibiting IC(50) values at the low micromolar level. As bisphosphonates are FDA clinically approved for treatment of bone resorption disorders, their potential innocuousness makes them good candidates to control tropical diseases.
Szajnman
Sergio H
SH
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Montalvetti
Andrea
A
Wang
Youhong
Y
Docampo
Roberto
R
Rodriguez
Juan B
JB
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004164:Diphosphonates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051228:Geranyltranstransferase; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
D004164:Diphosphonates; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase