MICROTUBULES AS THERAPEUTIC TARGET IN TRYPANOSOMA-BRUCEI-BRUCEI AND MOLINEMA-DESSETAE - ACTION OF 2-(AMINO-METHYL) ACRYLOPHENONE DERIVATIVES

2-(amino-methyl) acrylophenone derivatives as antimicrotubular agents were evaluated in vitro and in vivo against Trypanosoma brucei brucei and in vitro against infective larvae from the filaria Molinema desset ae. The compounds were active in vitro against T. b. brucei since the minimum effective concentrations were in a range from 22 to 35 mu M af ter one hour incubation time and in a range from 10 to 35 mu M after 2 4 hours incubation time. Nevertheless, no activity was recovered in vi vo for all the compounds at 50 mu moles/kg subcutaneously administered in a single dose. Moreover, interesting activity was obtained on M. d essetae infective larvae in vitro model since EC50 range were from 0.2 to 30 mu M after one day incubation time and from 0.2 to 1.5 mu M aft er seven days incubation time. No clear-cut correlation between antimi crotubular effect and biological activity emerged; the antimicrotubula r effect does not seem therefore the only mechanism of action for thes e compounds. Further pharmacomodulations could be studied to obtain be tter biovailability and lower toxicity.