Abstract Diterpenoid alkaloids are compounds of pharmacological interest. Forty four C 19 norditerp- enoid (NDAs) and 23 C 20 diterpenoid (DAs) alka- loids isolated from Aconitum, Delphinium and Consolida species were tested for their insecticidal effects (antifeedant and toxic) on Spodoptera littoralis and Leptinotarsa decemlineata, their cyto- toxicity on tumoral cell lines with several multidrug resistance mechanisms, and their antiparasitic effects against Trypanososma cruzi and Leishmania infan- tum. Overall, C 19 norditerpene alkaloids (NDAs) resulted better insect antifeedants and post-ingestive toxicants than the related C 20 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 nico- tininc insecticides. Among the most potent antifee- dants (EC 50 < 0.2 lg/cm 2 ) are the NDAs 1,14 diacetylcardiopetaline (10), 18-hydroxy-14-O-meth- ylgadesine (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-di- hydroatisine (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-oxocardiope- tamine (48) had a potent effect on T. cruzi epimastigotes. These compounds were not toxic to the host cell, significantly reduced parasite infec- tion capacity and severely affected the multiplica- tion 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. Keywords Aconitum Æ Consolida Æ Delphinium Æ Diterpenoid alkaloids Æ Insecticidal Æ Cytotoxic Æ Antiparasitic activity Æ Structure–activity relationships Abbreviations CPB Colorado potato beetle DA Diterpenoid alkaloid M. Reina Instituto de Productos Naturales y Agrobiologı ´a, IPNA, CSIC, La Laguna-Tenerife, Spain A. Gonza ´ lez-Coloma (&) Instituto de Ciencias Agrarias, ICA-CCMA, CSIC, C/ Serrano 115 dpdo., 28006 Madrid, Spain e-mail: azu@ccma.csic.es Phytochem Rev (2007) 6:81–95 DOI 10.1007/s11101-006-9013-5 123 Structural diversity and defensive properties of diterpenoid alkaloids Matı´as Reina Æ Azucena Gonza ´ lez-Coloma Received: 30 May 2006 / Accepted: 20 June 2006 / Published online: 6 March 2007 Ó Springer Science+Business Media B.V. 2007