Azasterols impair Giardia lamblia proliferation and induces encystation
- Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil)
- Laboratorio de Quimica Biologica, Centro de Biofisica y Bioquimica, Instituto Venezoelano de Investigaciones Cientificas, Caracas (Venezuela)
- Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF (United Kingdom)
The effects of sterol biosynthesis inhibitors on growth and fine structure of Giardia lamblia P1 strain cultures were analyzed. Azasterols demonstrated high efficacy in killing cells. The IC{sub 50} values for 22,26-azasterol and 24(R,S),25-epiminolanosterol were 7 {mu}M and 170 nM, respectively. Morphological analysis showed that azasterols induced changes in G. lamblia ultrastructure. The most significant alterations were: (a) considerable increase of the size of the peripheral vesicles, which are part of the parasite endosomal-lysosomal system; (b) appearance of autophagosomal structures; and (c) induction of differentiation, followed by an abnormal enlargement of encystation secretory vesicles. We propose that azasterols are effective chemotherapeutic drugs against Giardia lamblia in vitro and may have another target in cells besides sterol biosynthesis.
- OSTI ID:
- 21032973
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 363, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.08.174; PII: S0006-291X(07)01880-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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