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

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 (IC50) = 2.9 mu M] 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. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.