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Structural diversity and defensive properties of diterpenoid alkaloids

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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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Abbreviations

CPB:

Colorado potato beetle

DA:

Diterpenoid alkaloid

NDA:

Norditerpenoid alkaloid

PBO:

Piperonyl butoxide

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Acknowledgements

This work was partially supported by grants CICYT (DGES PB97-1265), MCYT (BQU2001-1505) and CAM (07M/0073/2002). We gratefully acknowledge S. Carlin for language revision.

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Authors and Affiliations

  1. Instituto de Productos Naturales y Agrobiología, IPNA, CSIC, La Laguna-Tenerife, Spain

    Matías Reina

  2. Instituto de Ciencias Agrarias, ICA-CCMA, CSIC, C/ Serrano 115 dpdo., 28006, Madrid, Spain

    Azucena González-Coloma

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  1. Matías Reina
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  2. Azucena González-Coloma
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Correspondence to Azucena González-Coloma.

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Reina, M., González-Coloma, A. Structural diversity and defensive properties of diterpenoid alkaloids. Phytochem Rev 6, 81–95 (2007). https://doi.org/10.1007/s11101-006-9013-5

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