Synthesis, cytotoxicity, and antileishmanial activity of N,N'-disubstituted ethylenediamine and imidazolidine derivatives

• Published in: TheScientificWorld 2010-09, Vol.10, p.1723-1730
• Main Authors: de Carvalho, Gustavo S G, Machado, Patrícia A, de Paula, Daniela T S, Coimbra, Elaine S, da Silva, Adilson D
• Format: Article
• Language: English
• Subjects: Animals; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Cell Survival - drug effects; Cells, Cultured; Chemical properties; Chemical synthesis; Composition; Ethylenediamines - chemical synthesis; Ethylenediamines - chemistry; Ethylenediamines - pharmacology; Identification and classification; Imidazole; Imidazolidines - chemical synthesis; Imidazolidines - chemistry; Imidazolidines - pharmacology; Leishmania - drug effects; Leishmania major - drug effects; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Methods; Mice; Mice, Inbred BALB C; Models, Chemical; Molecular Structure; Pharmaceutical chemistry; Production processes; Review
• ISSN: 1537-744X; 2356-6140; 1537-744X
• DOI: 10.1100/tsw.2010.176

This paper describes the preparation of N,N'-disubstituted ethylenediamine and imidazolidine derivatives and their in vitro biological activities against Leishmania species. Of the nine synthesized compounds, five displayed a good activity in both L. amazonensis and L. major promastigotes. The compounds 1,2-Bis(p-methoxybenzyl) ethylenediamine (4) and 1,3-Bis(p-methoxybenzyl)imidazolidines (5) showed the best activity on intracellular amastigotes, with IC50 values of 2.0 and 9.4 microgram/mL, respectively. In addition, none of compounds were cytotoxic against mammalian cells. The leishmanicidal activity can be related with inhibition of polyamine synthesis and cellular penetration within biological membranes.