title: Diamine and aminoalcohol derivatives active against Trypanosoma brucei.
abstract: Twenty compounds selected as representative members of three series of long-chain 1,2-diamines, 2-amino-1-alkanols and 1-amino-2-alkanols structurally related to dihydrosphingosin, were synthesized and tested in vitro for their ability to inhibit the sleeping sickness parasites Trypanosoma bruceirhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC(50) values in the submicromolar range, with selectivity indexes up to 39 related to the respective cytotoxicity values for Vero cells. The parasite phenotype detected after treatment with the most potent compounds showed irreversible cell morphology alterations of the flagellar pocket that lead to inhibition of cell growth and parasite death.
authors: Departamento de Química Farmacéutica, Facultad de Farmacia - CIETUS, Universidad de Salamanca, Campus Unamuno, E-37007 Salamanca, Spain. olmo@usal.es
authors: Esther Del
authors: ED
authors: Olmo
authors: Rosario
authors: R
authors: Diaz-González
authors: Ricardo
authors: R
authors: Escarcena
authors: Luis
authors: L
authors: Carvalho
authors: Luis A
authors: LA
authors: Bustos
authors: Miguel
authors: M
authors: Navarro
authors: Arturo San
authors: AS
authors: Feliciano
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000818:Animals; D016923:Cell Death; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002522:Chlorocebus aethiops; D003959:Diamines / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D010641:Phenotype; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000469:parasitology; D014709:Vero Cells
chemical_list: D000438:Alcohols; D003959:Diamines; D014344:Trypanocidal Agents