Antifeedant C20 Diterpene Alkaloids

Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Madrid, Spain
Chemistry & Biodiversity (Impact Factor: 1.52). 10/2004; 1(9):1327-35. DOI: 10.1002/cbdv.200490095
Source: PubMed


We have tested the insect antifeedant and toxic activity of 21 C20 diterpenoid alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedants to L. decemlineata and S. littoralis were the rearranged form of hetisine (20; EC50 = 1.7 microg/cm2) and 19-oxodihydroatisine (9; EC50 = 0.1 microg/cm2), resp. Glandulosine (8) moderately affected orally injected S. littoralis larvae. A few compounds (13-oxocardiopetamine (4), 9, and atisinium chloride (13)) had cytotoxic effects to insect-derived Sf9 cells with varying degrees of selectivity with respect to mammalian CHO cells. Compounds 4 and 15,22-O-diacetyl-19-oxodihydroatisine (10) increased Trypanosoma cruzi mortality. Our results support the plant protective role of C20 diterpenoid alkaloids and open a new field for parasite control strategies.

Download full-text


Available from: Rafael Alberto Martínez-Díaz, Oct 28, 2014
20 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Not Available
    Solid-State Circuits Conference, 1991. Digest of Technical Papers. 38th ISSCC., 1991 IEEE International; 03/1991
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The in vitro anti-proliferative effects are described of several atisine-type diterpenoid alkaloids against the protozoan parasite Leishmania infantum, which causes human visceral leishmaniasis and canine leishmaniasis in the Mediterranean basin, as well as human cutaneous leishmaniasis throughout the Mediterranean region. From a total of 43 compounds tested, including C19- and C20-diterpene alkaloids from several chemical classes, only 15,22-O-diacetyl-19-oxo-dihydroatisine, azitine and isoazitine were highly active against cultures of the parasite (promastigote form) with IC50 values within the range of the reference drug pentamidine-isothionate (7.39-12.80 mg/L for the test compounds, 11.32 mg/L for the positive control). These compounds were not toxic to the host cell. When treated with a dosage of 5 microg/mL of the active compounds (half of their IC50), the promastigote forms lost 80% of their infection capacity and the multiplication of extracellular forms of L. infantum was severely affected. The study showed that atisine-type C20-diterpenoid alkaloids exhibited promising anti-leishmanial properties with strong molecular selectivity. These might have implications for other intracellular pathogens- or phylogenetically related parasites, such as Trypanosoma spp.
    International Journal of Antimicrobial Agents 03/2005; 25(2):136-41. DOI:10.1016/j.ijantimicag.2004.08.010 · 4.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of natural products for the treatment of protozoal infections (Leishmania and Trypanosoma spp.) is well known and has been documented since ancient times. We have already established an in vitro culture system using mammalian host cells (Vero) infected with Trypanosoma cruzi in which the time course of parasite growth is determined quantitatively. This system was used to screen anti-T. cruzi agents using two experimental models: simultaneous cell infection and compound addition or preincubation of the parasite with the test compound prior to cell infection. Among 64 diterpenoid alkaloids tested, including C19 and C20 skeletons, five C20 compounds were active on T. cruzi epimastigotes: azitine, isoazitine and 15,22-O-diacetyl-19-oxodihydroatisine had moderate effects on the parasite, while atisinium chloride and 13-oxocardiopetamine were potent T. cruzi epimastigote growth inhibitors with activity levels similar to that of benznidazole, used as the reference drug. Additionally, these compounds decreased the ability of metacyclic forms to invade mammalian cells, their intracellular replications and their transformation into trypomastigotes, with no toxicity to the host cell. These results suggest that these alkaloids are structural leads of clinically active compounds against T. cruzi and probably other members of the Trypanosomatidae.
    Pharmacology 02/2006; 76(3):123-8. DOI:10.1159/000090600 · 1.67 Impact Factor
Show more