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

Abstract

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.