Structural diversity and defensive properties of diterpenoid alkaloids |
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Authors: | Matías Reina Azucena González-Coloma |
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Institution: | (1) Instituto de Productos Naturales y Agrobiología, IPNA, CSIC, La Laguna-Tenerife, Spain;(2) Instituto de Ciencias Agrarias, ICA-CCMA, CSIC, C/ Serrano 115 dpdo., 28006 Madrid, Spain |
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Abstract: | Diterpenoid alkaloids are compounds of pharmacological interest. Forty four C19 norditerpenoid (NDAs) and 23 C20 diterpenoid (DAs) alkaloids isolated from Aconitum, Delphinium and Consolida species were tested for their insecticidal effects (antifeedant and toxic) on Spodoptera littoralis and Leptinotarsa decemlineata, their cytotoxicity on tumoral cell lines with several multidrug resistance mechanisms, and their antiparasitic effects against
Trypanososma cruzi and Leishmania infantum. Overall, C19 norditerpene alkaloids (NDAs) resulted better insect antifeedants and post-ingestive toxicants than the related C20 diterpene alkaloids (DAs). Their antifeedant or insecticidal potencies did not parallel their reported nAChR binding activity,
but did correlate␣with the␣agonist/antagonist insecticidal/ antifeedant model proposed for nicotininc insecticides.␣Among
the most potent antifeedants (EC50 < 0.2 μg/cm2) are␣the NDAs 1,14 diacetylcardiopetaline (10),␣18-hydroxy-14-O-methylgadesine (34) and 14-O-acetyldelectinine (28) (to CPB) and the DA 19-oxodihydroatisine (55) (to S.␣littoralis). DAs had strong antiparasitic effects with molecular selectivity while NDAs were inactive. Delphigraciline (53), 15,22-O-Diacetyl-19-oxo-dihydroatisine (56), azitine (64) and isoazitine (65) were active against L. infantum promastigotes and had a moderate effect on T. cruzi epimastigotes, while atisinium chloride (59) and 13-oxocardiopetamine (48) had a potent effect on T. cruzi epimastigotes. These compounds were not toxic to the host cell, significantly reduced parasite infection capacity and severely
affected the multiplication of their extracellular forms. Several NDAs exhibited selective cytotoxicity to cancerous cells
and some of these had irreversible effects on SW480, HeLa and SkMel25 cell lines (neoline 5, pubescenine 16, 14-deacetylajadine 26, lycoctonine 27, dehydrotakaosamine 35, and ajadelphinine 38). These cytotoxic effects could be related to the inhibition of ATP production. |
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Keywords: | Aconitum Consolida Delphinium Diterpenoid alkaloids Insecticidal Cytotoxic Antiparasitic activity Structure– activity relationships |
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