Antimicrotubule benzimidazoles inhibit in vitro growth of Pneumocystis carinii.
Nine antimicrotubule benzimidazole derivatives tested in a Pneumocystis carinii culture system with human embryonic lung fibroblast monolayers inhibited organism proliferation. The concentrations of drugs inhibitory in culture ranged from 10 to 0.1 micrograms/ml, with thiabendazole being the least effective (10 micrograms/ml) and parbendazole being the most effective (0.1 microgram/ml). The parent compound, benzimidazole, was inactive at 10 micrograms/ml. Demonstration that this group of compounds has activity against P. carinii provides a new potential target that can be exploited, the microtubules. Also, the variability in the effectiveness of the compounds provides the basis for studies of structure-activity relationships, which were initiated in this study.
Bartlett
M S
MS
Indiana University School of Medicine, Indianapolis 46202-5250.
Edlind
T D
TD
Durkin
M M
MM
Shaw
M M
MM
Queener
S F
SF
Smith
J W
JW
D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects*; D011010:Pneumocystis / Q000187:drug effects* / Q000254:growth & development
D000981:Antiprotozoal Agents; D001562:Benzimidazoles