Apoptosis-like death in Leishmania donovani promastigotes induced by diospyrin and its ethanolamine derivative

Abstract

Previous studies have demonstrated that diospyrin ( 1), a quinonoid plant product, can inhibit the growth of Leishmania donovani parasites. Here, several derivatives of 1 were evaluated by the MTT assay and it was observed that the ethanolamine analogue ( 10) exhibited maximum cytotoxicity [50% inhibitory concentration (IC 50) = 2.9 μM] against L. donovani promastigotes. Subsequently, the mode of cell death in promastigotes was investigated through externalisation of membrane-associated phosphatidylserine, mitochondrial membrane depolarisation, DNA laddering and in situ labelling of DNA fragmentation by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) methods. Whilst both 1 and 10 were found to induce apoptosis-like death in promastigotes, the effect of 10 was evidently stronger even at a lower concentration. Hence, the ethanolamine derivative ( 10) of diospyrin ( 1) may be a prospective ‘lead’ for the development of novel cytotoxic agents inducing apoptosis in L. donovani parasites.