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 (IC(50))=2.9 microM] 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.
Mukherjee
Piyali
P
Department of Microbiology, Bose Institute, Calcutta, India.
Majee
Sutapa Biswas
SB
Ghosh
Subhalakshmi
S
Hazra
Banasri
B
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis; D053938:DNA Fragmentation; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests
D000981:Antiprotozoal Agents; D004983:Ethanolamines; D009285:Naphthoquinones; C043546:diospyrin