Antifeedant and toxic effects of drimanes on Colorado potato beetle larvae

Among the drimane compounds tested, the dialdehydes polygodial and warburganal were the most active as antifeedants against Colorado potato beetle larvae, Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae), in a dual-choice assay with potato, Solanum tuberosum L., leaf discs. Lactones were less effective. Direct observations showed that decreased feeding on leaf discs treated with polygodial and warburganal was accompanied by increased locomotry activity. Topical application of these two compounds on the insect's cuticle decreased food intake of untreated leaf discs, indicating that besides deterrent effects, toxic properties of these molecules influence feeding behaviour.     

(−)-3β-Acetoxydrimenin from the leaves of Drimys winteri

A new natural product, 3β-acetoxydrimenin was isolated from the petrol extract of the leaves of Drimys winteri which also contains the known compounds safrol, drimenol and polygodial. The structure of the new compound was determined by chemical and spectroscopic methods.     

Drimanes from Drimys brasiliensis with leishmanicidal and antimalarial activity

This paper evaluates CHCl₃ and CH₃OH extracts of the stem bark, branches and leaves of Drimys brasiliensis and drimane sesquiterpenes isolated from the stem bark against strains of Leishmania amazonensis and Leishmania braziliensis promastigotes and Plasmodium falciparum trophozoites. All of the extracts and compounds were tested in cell lines in comparison with reference standards and cell viability was determined by the XTT method. The CHCl₃ and CH₃OH extracts from the stem bark and branches yielded promising results against two strains of Leishmania, with 50% inhibitory concentrations (IC₅₀ ) values ranging from 39-100 µg/mL. The CHCl₃ extract of the stem bark returned IC₅₀ values of 39 and 40.6 µg/mL for L. amazonensis and L. braziliensis, respectively. The drimanes were relatively effective: 1-β-(p-coumaroyloxy)-polygodial produced IC₅₀ values of 5.55 and 2.52 µM for L. amazonensis and L. braziliensis, respectively, compared with 1-β-(p-methoxycinnamoyl)-polygodial, which produced respective IC₅₀ values of 15.85 and 17.80 µM. The CHCl₃ extract demonstrated activity (IC₅₀ of 3.0 µg/mL) against P. falciparum. The IC₅₀ values of 1-β-(p-cumaroyloxyl)-polygodial and 1-β-(p-methoxycinnamoyl)-polygodial were 1.01 and 4.87 µM, respectively, for the trophozoite strain. Therefore, the results suggest that D. brasiliensis is a promising plant from which to obtain new and effective antiparasitic agents.     

栓菌Trametes sp. G048的化学成分研究

从栓菌属真菌Trametes sp. G048的发酵液和菌丝体中分离并鉴定出6个化合物,经波谱数据分析分别鉴定为isodrimenediol diacetate(1)i、sodrimenediol 2-acetate(2)、脑苷脂D(3)、麦角甾醇(4)、过氧化麦角甾醇(5)和啤酒甾醇(6)。其中化合物1和2为新的天然产物。     

Terpenoids from the liverwort Blepharostoma trichophyllum

Blepharostol, a new sesquiterpenoid alcohol with a rearranged drimane skeleton and five new ent-labdane diterpenoids, ent-labda-13(16),14-diene-8alpha-ol, ent-labda-13(16),14-diene-1beta,8alpha-diol, ent-labda-13(16),14-diene-8alpha,9beta-diol, ent-labda-13(16),14-diene-1beta,8alpha,9beta-triol and ent-8alpha,9beta-dihydroxylabda-13(16),14-dien-1-one, have been isolated from the liverwort Blepharostoma trichophyllum. Their structures have been assigned on the basis of their spectroscopic properties.     

Behavioural and sensory responses to drimane antifeedants in Pieris brassicae larvae

Fifteen drimane compounds were tested for their feeding inhibiting activity in larvae of Pieris brassicae L. (Lepidoptera: Pieridae) when applied to leaf material of the host plant Brassica oleracea L. The antifeedant efficacy of the drimanes was related to their molecular structure in order to identify important functional groups. Of the drimanes tested, those with a lactone group on the B-ring were the most effective feeding inhibitors. Additionally, the sensory responses to 13 of the drimanes were measured. Neural activity was evoked in the deterrent cell in the medial sensillum styloconicum. Also, inhibition of sensory responses to feeding stimulants was found. Results of behavioural and electrophysiological tests were correlated in an attempt to elucidate the sensory code underlying feeding inhibition by drimanes in Pieris brassicae. It was concluded that the response of the deterrent cell in the medial sensillum styloconicum contributes significantly to inhibition of feeding behaviour in larvae of Pieris brassicae.     

Cyclohexenone Derivative and Drimane Sesquiterpenes from the Seagrass-Derived Fungus Aspergillus insuetus

One new cyclohexenone derivative ( 1 ), and two undescribed drimane sesquiterpenes ( 2 and 3 ), together with another seven known drimane sesquiterpenes were isolated from a seagrass-derived fungus Aspergillus insuetus SYSU6925. Structures of these metabolites were elucidated by comprehensive spectroscopic analysis, including NMR analysis, mass spectrometry, and ECD calculations. Compounds 1 – 3 , 5 and 7 displayed weak to moderate antifungal activities towards four phytopathogenic fungi, with Minimum inhibition concentration (MIC) values range from 50 to 200 μg/mL. Compound 1 , a rare cyclohexenone derivative with n-propyl group exhibited more potent inhibitory activities (MIC, 50 μg/mL) against F. oxysporum than positive control (Triadimefon). Compounds 2 and 3 also exhibit potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in RAW264.7 cells with IC₅₀ values of 21.5±1.1 and 32.6±1.16 μM, respectively.     

Behavioural observations of Pieris brassicae larvae indicate multiple mechanisms of action of analogous drimane antifeedants

We tested 11 analogous synthetic drimane antifeedant compounds for their feeding inhibiting effects on larvae of the large white butterfly Pieris brassicae L. (Lepidoptera: Pieridae) in no-choice tests on the host plant Brassica oleracea L. Furthermore, we observed larval feeding behaviour in no-choice tests to analyze temporal effects of five drimanes. The results show that the five analogous antifeedants differentially influence feeding behaviour and locomotion activity. Warburganal and polygodial are most likely sensory mediated antifeedants. Habituation to these compounds occurs soon after the onset of the tests (i.e., within 0.5–1.5 h). Compound 5 and confertifolin are probably not direct, sensory mediated antifeedants. After 0.5–1.5 h of exposure, these compounds inhibit not only feeding, but also locomotion behaviour, indicating postingestive, toxic effects. Isodrimenin inhibits feeding from the onset of the test and is probably a sensory mediated antifeedant. No habituation occurs to this compound, indicating that isodrimenin is either a very strong antifeedant or that it additionally has postingestive, toxic effects. Topical application of the drimanes on the larval cuticle revealed feeding inhibiting effects, but these could not be related to the occurrence of postingestive feeding inhibiting effects, indicating that this method is inappropriate to show possible postingestive effects of drimanes in P. brassicae. In conclusion, the behavioural observations performed in this research indicate that analogous drimanes inhibit feeding by P. brassicae larvae through multiple mechanisms of action. The results show that, when developing a structure activity relationship (SAR) for a series of antifeedants, it is important to distinguish the mode of action which underlies inhibition of feeding.     

Caspases and receptor cleavage

In addition to their established functions in programmed cell death, there is increasing evidence that caspases contribute to several other cellular processes beside of apoptosis. So-called "dependence receptors" represent a group of receptors, which derive from different protein families, but are functionally linked by their capability to regulate cell survival in presence of their respective ligands thereby preserving cellular homeostasis. In the absence of their ligands these receptors are cleaved by caspases thereby releasing pro-apoptotic receptor fragments (e.g. rearranged during transfection [RET]) or permitting the exposure of death domains, which were masked before through other receptor domains (e.g. deleted in colorectal carcinoma [DCC]). Apart from these, there are other plasma membrane receptors such as the epidermal growth factor receptor, which have been identified as substrates of caspases. In terms of signal-transduction, caspase-mediated cleavage of these receptors blocks ligand-induced activation of their intracellular signalling. It is hypothesized that this might be another mechanism, whereby caspases trigger cell toxicity through shut-down of survival signals.     

Identification of a drimenol synthase and drimenol oxidase from Persicaria hydropiper,involved in the biosynthesis of insect deterrent drimanes

The sesquiterpenoid polygodial, which belongs to the drimane family, has been shown to be an antifeedant for a number of herbivorous insects. It is presumed to be synthesized from farnesyl diphosphate via drimenol, subsequent C‐12 hydroxylation and further oxidations at both C‐11 and C‐12 to form a dialdehyde. Here, we have identified a drimenol synthase (PhDS) and a cytochrome P450 drimenol oxidase (PhDOX1) from Persicaria hydropiper. Expression of PhDS in yeast and plants resulted in production of drimenol alone. Co‐expression of PhDS with PhDOX1 in yeast yielded drimendiol, the 12‐hydroxylation product of drimenol, as a major product, and cinnamolide. When PhDS and PhDOX1 were transiently expressed by agro‐infiltration in Nicotiana benthamiana leaves, drimenol was almost completely converted into cinnamolide and several additional drimenol derivatives were observed. In vitro assays showed that PhDOX1 only catalyses the conversion from drimenol to drimendiol, and not the further oxidation into an aldehyde. In yeast and heterologous plant hosts, the C‐12 position of drimendiol is therefore likely to be further oxidized by endogenous enzymes into an aldehyde and subsequently converted to cinnamolide, presumably by spontaneous hemiacetal formation with the C‐11 hydroxyl group followed by oxidation. Purified cinnamolide was confirmed by NMR and shown to be deterrent with an effective deterrent dose (ED₅₀) of about 200–400 μg g^?1 fresh weight against both whiteflies and aphids. The putative additional physiological and biochemical requirements for polygodial biosynthesis and stable storage in plant tissues are discussed.