In vitro activity of 10-deacetylbaccatin III against Leishmania donovani promastigotes and intracellular amastigotes.
Current treatments for leishmaniasis are unsatisfactory due to their route of administration, toxicity and expense but, most importantly, to the developed resistance of Leishmania to first-line drugs. Therefore, the identification of new effective targeted drugs is an urgent need. Since many studies have shown that medicinal plants contain compounds active against protozoa we have undertaken a study aiming to determine the antileishmanial activity of the taxoid 10-deacetylbaccatin III, isolated from dried needles and small branches of the European yew tree (Taxus baccata). Interestingly, 10-deacetylbaccatin III was found to selectively inhibit the growth of L. DONOVANI intracellular amastigotes within J774 murine macrophages in vitro at nanomolar concentrations with an IC(50) value of 70 nM. Concentrations of 10-deacetylbaccatin III as high as 5 microM did not affect J774 murine macrophages whereas 20 nM of taxol, used as a control, was toxic to macrophages. The compound also inhibited the growth of L. donovani promastigotes but at higher concentrations with a maximum level of inhibition of 35 %. Taxol inhibited promastigote growth at micromolar concentrations. Comparison of the effect of 10-deacetylbaccatin III to that of taxol on cell cycle progression and cellular morphology showed that their mechanisms of action are different. The 10-deacetylbaccatin III-treated promastigotes were slightly arrested in the G2/M phase whereas taxol-treated cells were blocked in the G2/M phase. In addition 10-deacetylbaccatin III treatment, contrary to taxol, did not affect cellular morphology.
Georgopoulou
Katerina
K
Laboratory of Molecular Parasitology, Department of Microbiology, Hellenic Pasteur Institute, Athens, Greece.
Smirlis
Despina
D
Bisti
Sylvia
S
Xingi
Evangelia
E
Skaltsounis
Leandros
L
Soteriadou
Ketty
K
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007893:Leishmania donovani / Q000187:drug effects* / Q000502:physiology; D007896:Leishmaniasis / Q000188:drug therapy; D009339:Needles; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020946:Taxus
D000981:Antiprotozoal Agents; D010936:Plant Extracts; D043823:Taxoids; C042213:10-deacetylbaccatine III