Abstract | BACKGROUND: PURPOSE: METHODS: The effect of the isolated compounds (DCTN, CTN and AAA) from the bark of C. cajucara was assessed in vitro against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis by counting of remaining parasites in a Neubauer chamber in comparison to pentamidine used as standard drug. The action of natural products on trypanothione reductase was assessed using soluble protein fraction of promastigotes. The assays were performed by incubation with HEPES, EDTA, NADPH and trypanothione disulfide to quantify the NAPH consumption by TryR. RESULTS: The results showed very high efficacy, especially of the diterpene DCTN, against promastigotes (IC50 = 6.30 ± 0.06 µg/ml) and axenic amastigotes (IC50 = 19.98 ± 0.05 µg/ml) of L. amazonenesis. The cytotoxic effect of the best active natural product was evaluated on mouse peritoneal infected macrophages (IC50 = 0.47 ± 0.03 µg/ml in 24 h of culture), and the treatment revealed that DCTN never reaches toxic concentrations while reducing the infection and, most importantly, with no toxicity (>100 µg/ml with 0% of macrophage kill) when compared to pentamidine (37.5 µg/ml with 100% of macrophage kill). Furthermore, all of the natural products assayed on the trypanothione reductase enzyme inhibited the enzyme activity compared to the control. CONCLUSION:
Clerodane diterpenes from C. cajucara showed promising in vitro antileishmanial effects against L. amazonensis, specially the DCTN with no macrophage toxicity up to the assayed concentration. In addition, the action on trypanothione reductase enzyme revealed a possible mechanism of action.
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Authors | Gerson S Lima, Denise B Castro-Pinto, Gerzia C Machado, Maria A M Maciel, Aurea Echevarria |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 22
Issue 12
Pg. 1133-7
(Nov 15 2015)
ISSN: 1618-095X [Electronic] Germany |
PMID | 26547537
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier GmbH. All rights reserved. |
Chemical References |
- Antiprotozoal Agents
- Diterpenes
- Diterpenes, Clerodane
- Triterpenes
- dehydrocrotonin
- trans-crotonin
- acetylaleuritolic acid
- NADH, NADPH Oxidoreductases
- trypanothione reductase
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Topics |
- Animals
- Antiprotozoal Agents
(isolation & purification, pharmacology)
- Croton
(chemistry)
- Diterpenes
- Diterpenes, Clerodane
(isolation & purification, pharmacology)
- Inhibitory Concentration 50
- Leishmania
(drug effects)
- Macrophages, Peritoneal
(drug effects, parasitology)
- Medicine, Traditional
- Mice
- Mice, Inbred BALB C
- Molecular Structure
- NADH, NADPH Oxidoreductases
(antagonists & inhibitors)
- Plant Bark
(chemistry)
- Triterpenes
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