Structural Diversity and Defensive Properties of Norditerpenoid Alkaloids

Abstract

We have tested the insect antifeedant and toxic activity of 43 norditerpenoid alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata including eserine (physostigmine), anabasine, and atropine. Antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedants to L. decemlineata were 1,14-diacetylcardiopetaline (9) and 18-hydroxy- 14-O-methylgadesine (33), followed by 8-O-methylconsolarine (12), 14-O-acetyldelectinine (27), karakoline (7), cardiopetaline (8), 18-O-demethylpubescenine (13), 14-O-acetyldeltatsine (18), takaosamine (21), ajadine (24), and 8-O-methylcolumbianine (6) (EC50 < 1 microg/cm2). This insect showed a moderate response to atropine. S. littoralis had the strongest antifeedant response to 24, 18, 14-O-acetyldelcosine (19), and delphatine (29) (EC50 < 3 microg/cm2). None of the model substances affected the feeding behavior of this insect. The most toxic compound to L. decemlineata was aconitine (1), followed by cardiopetalidine (10) (% mortality > 60), 14-deacetylpubescenine (14), 18-O-benzoyl-18-O-demethyl-14-O-deacetylpubescenine (17), 14-O-acetyldelcosine (19), 14-deacetylajadine (25) and methyllycaconitine (30) (% mortality > 45). Orally injected S. littoralis larvae were negatively affected by 1, cardiopetaline (8), 10, 1,14-O-acetylcardiopetalidina (11), 12, 14, 1,18-O-diacetyl-19-oxo-gigactonine (41), olivimine (43), and eserine in varying degrees. 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. A few compounds [14, tuguaconitine (38), 14-demethyldelboxine (40), 19, dehydrodelsoline (36), 18-O-demethylpubescenine (13), 41, 9, and delcosine (23)] had selective cytotoxic effects to ward insect-derived Sf9 cells. None were cytotoxic to mammalian CHO cells and none increased Trypanosoma cruzi mortality. The selective cytotoxic effects of some structures indicate that they can act on biological targets other than neuroreceptors.

Secondary metabolites in floral nectar reduce parasite infections in bumblebees

“…The only cost of anabasine consumption we detected was a 2-day delay in onset of egg laying, with no effect on the eventual number or mass of eggs and larvae. These results are in contrast to studies showing lethal and sublethal effects of anabasine on other insects [47]. Moreover, although bumblebees are known to be deterred from feeding by some secondary metabolites in nectar and pollen [48,49], bees in this experiment increased rather than decreased consumption of nectar containing a high concentration (20 ppm) of anabasine.…”

In vitro activity of C20-diterpenoid alkaloid derivatives in promastigotes and intracellular amastigotes of Leishmania infantum

“…Previous results have shown that T. cruzi mortality increased with ADs 13-oxo-cardiopetamine (inactive against L. infantum, data not shown) and 1, while 2 and 3 were inactive which suggests species-related selectivity for the anti-parasitic action of these compounds, with L. infantum being more sensitive to DAs than T. cruzi. Furthermore, none of 43 NDAs tested on T. cruzi affected its viability as shown here for L. infantum [10,15] indicating a strong molecular selectivity for the trypanocidal and leishmanicidal effect of DAs.…”

“…NDAs act as potent nicotinic cholinergic receptor (nAcChR) agonists and antagonists in invertebrates, including insects and in vertebrates [7]. The insecticidal and anti-feedant activity of NDAs [8][9][10], suggest a defensive role played by these compounds. However, only a few DAs have been studied for their plant defensive and pharmacological properties, including their effects on Trypanosoma cruzi epimastigote forms [9,[11][12][13][14][15] and their neurotoxic effects are unknown.…”

Diterpenoid alkaloids from some Turkish Consolida species and their antiviral activities

“…In this study, in vitro antiviral, antibacterial, and antifungal activities of five diterpene-type of alkaloids (1)(2)(3)(4)(5) were determined ( Figure 1). The results pointed out that these alkaloids possessed the highest antibacterial activity against K. pneumoniae and A. baumannii (Table 1) at 8 µg/ml concentration, whereas they were moderately active to the rest of the bacteria.…”

“…1 These plants have also been the cause of poisonings that primarily occur in cattle as well as human beings, due to toxicity of their alkaloids. [2][3][4][5] The common name of Consolida sp., shared with the closely related genus Delphinium, is "larkspur".…”