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.