Synthesis and in Vitro Leishmanicidal Effects of Conformationally Restricted Analogues of Pentamidine

Four conformationally restricted analogues of pentamidine were prepared. then, different concentrations (0.039, 0.078, 0.156, 0.312 and 0.625 mg/ml) of each compound and two positive controls (amphotericin b and pentamidine, 0.625 mg/ml), one negative control (culture medium) and one solvent control (dmso) were prepared and placed in 24-well plates containing 50000 parasite per well. promastigotes of leishmania major were incubated over a period of 2 days at 25°c; subsequently, percent of viable parasite in each well determined spectrophotometrically using mtt assay. the average ec50 for compounds 4a,b and 8a,b in dmso was 0.098, 0.410, 0.150, 0.720 mg/ml, respectively. the average ec50 for positive controls pentamidine and amphotericin b was found to be 0.062 and 0.026 mg/ml. the control solvent had no significant effect on l. major promastigotes. all compounds had significant effect compared to dmso and were less potent than positive controls.