Diamine and aminoalcohol derivatives active against Trypanosoma brucei
摘要:
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 brucei rhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC50 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. (C) 2011 Elsevier Ltd. All rights reserved.
Diamine and aminoalcohol derivatives active against Trypanosoma brucei
作者:Esther del Olmo、Rosario Diaz-González、Ricardo Escarcena、Luis Carvalho、Luis A. Bustos、Miguel Navarro、Arturo San Feliciano
DOI:10.1016/j.bmcl.2011.10.108
日期:2012.1
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 brucei rhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC50 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. (C) 2011 Elsevier Ltd. All rights reserved.