Síntese de diaminas e amino álcoois, potenciais agentes leishmanicidas

Abstract

Leishmaniasis is an infection caused by protozoan parasites belonging to the genius Leishmania. This disease is endemic to the American, Asian and African tropical countries with an estimated 1.5-2 million cases per year in about 88 countries. The severity of the disease species varies widely and the clinical manifestations in human occur in three major forms: the most common cutaneous leishmaniasis; mucocutaneous leishmaniasis, causing tissue damages to nose and mouth; and the most serious visceral leishmaniasis, which is fatal if untreated. Aiming the development of new molecules which can act as leishmanicidal agents, we describe in this work the preparation, characterization and leishmanicidal evaluation of several N-alkyl diamines and amino alcohols, bearing different carbonic chains. These diamines and amino alcohols were obtained from long chains alcohols or n octyl chloride. These alcohols were initially treated with methanesulfonyl chloride in dichlorometane and pyridine, leading to the corresponding alkyl mesylates. The diamines and amino alcohols were prepared by substitution of the mesyl group or of chlorine atom of n octyl chloride by diamines (1,2-ethanediamine, 1,3-propanediamine, 1,4-butanediamine or 1,6-hexanediamine) or amino alcohols (2-amino-ethanol, 3-amino-1-propanol, diethanolamine or 2-amino-2-methyl-1-propanol). The structures of the obtained compounds were elucidated by infrared spectroscopy, 1H and 13C NMR. The diamines and amino alcohols derivated from 1-dodecanol showed a very good activity against L. amazonensis and L. chagasi. Compound N-dodecyl-1,2- ethanediamine and N-decyl-1,3-propanediamine were 7.3 and 2.6 times, respectively, more active than the reference drug amphotericin B against L. chagasi promastigote form.