Synthesis and antileishmanial activity of 3-(alpha-azolylbenzyl)indoles.

The goal of the present study was to evaluate several azolyl-substituted indoles as new antileishmanial agents. Ten 3-(alpha-azolylbenzyl)indoles have been synthesized using Friedel-Crafts acylation as a key-step. All the target compounds were found to display high levels of activity when tested against Leishmania mexicana promastigotes in vitro.

In vitro and in vivo antileishmanial activity of 2-amino-4,6-dimethylpyridine derivatives against Leishmania mexicana.

Leishmania mexicana promastigote and intracellular amastigote growths were inhibited by the water-soluble furan-2-carboxamide issued from the pharmacophore 2-amino-4,6-dimethylpyridine with IC50 values of 69 +/- 2 and 89 +/- 9 microM, respectively. This compound was also tested against established L. mexicana infection in susceptible BALB/c mice; an intraperitoneal administration of 10 mg/Kg/day during five consecutive days induced a high reduction in the amastigote burden of the poplitea lymph node (81 +/- 6.

Synthesis and antileishmanial activity of new 1-(pyridin-2-yl)imidazolidin-2-ones derived from 2-amino-4,6-dimethylpyridine.

Derivatives of 2-amino-4,6-dimethylpyridine resulting from the integration of the amino function into a 2-imidazolidinone were synthetized via the corresponding 2-chloroethylurea. N3-benzylation, acylation or sulfonylation afforded the target compounds 6-14 which were evaluated for their in vitro and in vivo antileishmanial activity. Two compounds, the N3-benzyl derivative 7 and the N3-tolylsulfonyl derivative 14, exhibited potent inhibition against cultured extracellular promastigotes of Leishmania mexicana with IC50 comparable to that of the previously studied N-(4,6-dimethylpyridin-2-yl) furan-2-carboxamide 2: 32.

A glycoprotein isolated from the sponge, Pachymatisma johnstonii, has anti-leishmanial activity.

A high anti-leishmanial activity was observed in an aqueous extract from the marine sponge Pachymatisma johnstonii, Bowerbank 1842 (Demospongiae, Geodiidae). Pachymatismin, a glycoprotein, was purified and shown to be a cytotoxic agent, which acts on promastigote and clinical-like amastigote stages with IC50 about 1 microg protein/ml and induces changes in the cell shape, phospholipase A2 activity and invasion capacity of the parasite. We believe pachymatismin is the first reported substance from a marine organism with anti-leishmanial activity.