Antifeedant C20 diterpene alkaloids

We have tested the insect antifeedant and toxic activity of 21 C20 diterpenoid alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedants to L. decemlineata and S. littoralis were the rearranged form of hetisine (20; EC50 = 1.7 microg/cm2) and 19-oxodihydroatisine (9; EC50 = 0.1 microg/cm2), resp. Glandulosine (8) moderately affected orally injected S. littoralis larvae. A few compounds (13-oxocardiopetamine (4), 9, and atisinium chloride (13)) had cytotoxic effects to insect-derived Sf9 cells with varying degrees of selectivity with respect to mammalian CHO cells. Compounds 4 and 15,22-O-diacetyl-19-oxodihydroatisine (10) increased Trypanosoma cruzi mortality. Our results support the plant protective role of C20 diterpenoid alkaloids and open a new field for parasite control strategies.     

Antifeedant and phytotoxic activity of hydroxyperezone and related molecules

The insect antifeedant and toxic activity of hydroxyperezone (1), its derivatives 2-9, along with 3-hydroxy- (10) and 6-hydroxythymoquinone (11) were studied against Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. The antifeedant tests showed that L. decemlineata was the most sensitive insect, followed by M. persicae, while S. littoralis was not deterred by compounds 1-11. Leucohydroxyperezone tetraacetate (3), oxoperezinone (6), dihydroleucoperezinone diacetate (7), 3-hydroxy- (10) and 6-hydroxythymoquinone (11) showed strong activity against L. decemlineata. 1 and 7 exhibited moderate deterrent activity against M. persicae, while 1 and dihydroleucohydroxyperezone tetraacetate (4) acted as post-ingestive antifeedants to S. littoralis. The phytotoxic activity of compounds 1-11 was also evaluated. Hydroxyperezone (1) strongly inhibited seed germination at 24 h, while the activity of 3-8 and 10 was moderate. The level of radicle growth inhibition obtained with compounds 1-5 and 8-11 was significant (< 50%).     

Antifeedant and phytotoxic activity of cacalolides and eremophilanolides

The antifeedant effect of six cacalolides and six eremophilanolides was tested against the herbivorous insects Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. The test compounds included several natural products isolated from Senecio madagascariensis (14-isovaleryloxy-1,2-dehydrocacalol methyl ether, 4), S. barba-johannis (13-hydroxy-14-oxocacalohastine, 5; 13-acetyloxy-14-oxocacalohastine, 6) and S. toluccanus [6-hydroxyeuryopsin, 7; 1(10)-epoxy-6-hydroxyeuryopsin, 9; toluccanolide A, 11] and the derivatives cacalol methyl ether (1); cacalol acetate (2); 1-acetyloxy-2-methyloxy-1,2,3,4-tetradehydrocacalol acetate (3); 6-acetyloxyeuryopsin (8); 6-acetyloxy-1(10)-epoxyeuryopsin (10), and toluccanolide A acetate (12). Compound 11 and its derivative 12 exhibited moderate antifeedant activity against S. littoralis; 2, 7-10, and 12 showed strong activity against L. decemlineata, while the aphid M. persicae was moderately deterred in the presence of compounds 1, 4, 8, 10, and 12. The phytotoxic activity of 1-12 on Lactuca sativa was also evaluated. Compounds 2 and 4-12 moderately inhibited seed germination at 24 h, while compounds 1-4, 6, 9, and 10 had a significant inhibition effect on L. sativa radicle length (over 50%).     

Selective action of acetogenin mitochondrial complex I inhibitors

Five annonaceous acetogenins, rolliniastatin-1 [structure: see text], rolliniastatin-2 [structure: see text], laherradurin [structure: see text], squamocin [structure: see text], annonacin [structure: see text], and rotenone as a reference, differing in their NADH oxidase inhibition activity, have been evaluated for antifeedant, insecticidal, trypanocidal and cytotoxic effects on insect, mammalian and tumor cells. All the test compounds were toxic to Leptinotarsa decemlineata, demonstrated selective cytotoxicity to insect Sf9 cells and a panel of tumor cell lines with the multidrug-resistant SW480 (P-glycoprotein+, Pgp+) being the most sensitive one. Compounds [structure: see text] and rotenone had post-ingestive effects against Spodoptera littoralis larvae while [structure: see text] and rotenone were active against Trypanosoma cruzi. Based on their biochemical properties (inhibition of the mitochondrial NADH oxidase activity), the in vivo effects of these compounds on S. littoralis and their cytotoxic effects on Sf9 and tumor cells were more predictable than their effect on T. cruzi and mammalian cells.     

Antifeedant activity of some polygodial derivatives

Polygodial (1) and its derivatives acetal 2 (propylene) and 3 (ethylene) were prepared and their antifeedant activity and toxic effects evaluated on several insect species with different feeding ecologies (Spodoptera littoralis, Leptinotarsa decemlineata, Myzus persicae and Rhopalosiphum padi) along with that of polygonone (4). We also tested their selective cytotoxic effects on insect-derived (Spodoptera frugiperda ovarian Sf9 cells) and mammalian Chinese hamster ovary (CHO) cells. The antifeedant activity of these compounds was consistent with the proposed mode of action for antifeedant drimanes, i. e. adduct formation with amino groups for M. persicae and R. padi (dialdehyde > ketoaldehyde > aldehydeacetal). This was not the case for L. decemlineata, and the cytotoxic effects on insect-derived Sf9 and mammalian CHO cells (aldehydeacetal > dialdehyde > ketoaldehyde).     

Antifeeding Active Substances for Insect in Caryopteris divaricata Maxim.

Six antifeeding active diterpenes having a clerodane skeleton, clerodin (I), caryoptin (II), dihydroc?erodin-I (V), dihydrocaryoptin (VI), clerodin hemiacetal (VII), and caryoptin hemi- acetal (VIII), were isolated from Caryopteris divaricata Maxim. Antifeeding activities of six compounds and these derivatives against the 3rd instar larvae of Spodoptera litura F. were tested by the leaf disk method. In addition, the terms of “relative antifeedant” and “absolute antifeedant” were proposed for the antifeeding substances, and the latter term was used to the above six diterpenes.     

Antifeedant activity of fatty acid esters and phytosterols from Echium wildpretii

Crude extracts and fractions from Echium wildpretii H. Pearson ex Hook. f. subsp. wildpretii (Boraginaceae) have been tested against insect species Spodoptera littoralis, Leptinotarsa decemlineata, and the aphids Myzus persicae, Diuraphis noxia, Metopolophium dirhodum, Rhopalosiphum maidis, and Rhopalosiphum padi. The EtOH extract and the lipid and steroidal fractions of E. wildpretii exhibited significant antifeedant activities against the aphids and L. decemlineata. Two bioactive mixtures composed of fatty acid esters and n-alkanes were obtained from the lipid fraction. The bioguided fractionation of the steroidal fraction resulted in the isolation of glutinol, β-sitosterol, (3β,7α)-stigmast-5-ene-3,7-diol, and (3β,7α)-7-methoxystigmast-5-en-3-ol. The latter two compounds exhibited potent antifeedant activities against L. decemlineata indicating that the presence of an O-bearing C(7) was responsible for the activities of these molecules.     

Effects of ajugarins and related neoclerodane diterpenoids on feeding behaviour of Leptinotarsa decemlineata and Spodoptera exigua larvae

Three naturally occurring ajugarins and seven semisynthetic derivatives of them, possessing different functionalities in the decalin part, together with two natural furoneoclerodane diterpenes, have been assessed as feeding behavior modifying agents of larvae of the generalist Spodoptera exigua and a specialist like Leptinotarsa decemlineata. Ajugarin I and some of its derivatives exhibited a significant antifeedant activity against larvae of S. exigua in both choice and no-choice assays. Conversely, the furoneoclerodane diterpenes only presented antifeedant activity against larvae of L. decemlineata. These results indicate that the biological action of the tested substances is strongly modulated by minimal structural variations, which are also responsible for the specificity of action.     

Insect antifeedants, pterocarpans and pterocarpol, in heartwood of Pterocarpus macrocarpus Kruz

The insect antifeedant activities of pterocarpans and a sesquiterpene alcohol from the dichloromethane extract of Pterocarpus macrocarpus Kruz. (Leguminosae) were evaluated against the common cutworm, Spodoptera litura F. (Noctuidae), and the subterranean termite, Reticulitermes speratus (Kolbe)(Rhinotermitidae). Three pterocarpans, (-)-homopterocarpin (1), (-)-pterocarpin (2), and (-)-hydroxyhomopterocarpin (3) and the sesquiterpene alcohol, (+)-pterocarpol (5), were isolated from the dichloromethane extract of the heartwood of P. macrocarpus under guidance by a biological assay. Among these natural products, the most active insect antifeedant against both S. litura and R. speratus was 1. On the other hand, sesquiterpene alcohol 5 showed less insect antifeedant activity than the other pterocarpans against both insect species. While its methylated derivative, (-)-methoxyhomopterocarpin (4), showed high biological activity, 3 showed less insect antifeedant activity in this study. Interestingly, racemic 1 did not show insect antifeedant activity against S. litura. However, all of the test pterocarpans and isoflavones showed antifeedant activity against the test termites. Additionally, since these compounds were major constituents of P. macrocarpus, these antifeedant phenolics may act as chemical defense factors in this tree. In Thailand, lumber made from this tree is used to make furniture and in building construction due to its resistance to termite attack.     

Casearin X,Its Degradation Product and Other Clerodane Diterpenes from Leaves of Casearia sylvestris: Evaluation of Cytotoxicity against Normal and Tumor Human Cells

An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F. Casearin X degraded to the corresponding dialdehyde when stored in CDCl₃. The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC₅₀ values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity.     

Eudesmanolides and Other Constituents from the Flowers of Wedelia trilobata

Two eudesmane sesquiterpene lactones, wedetrilides B ( 1 ) and C ( 2 ), along with five known analogues ( 3 – 8 ), an ent‐kaurane diterpenoid ( 9 ), a steroid ( 10 ), as well as cinnamic acid derivatives ( 11 – 13 ), were isolated from the flowers of Wedelia trilobata. Their structures were elucidated on the basis of extensive spectroscopic analyses and by comparison of their NMR data with those of related compounds. Furthermore, the structures of 1 and 3 – 5 were confirmed by X‐ray single‐crystal diffraction analyses. Compounds 4 and 5 exhibited weak cytotoxic activities against the MCF‐7, HeLa, and A549 cell lines. Compounds 3 – 5 were also evaluated for their inhibitory effects against HIV lytic replication.     

Antibacterials and modulators of bacterial resistance from the immature cones of Chamaecyparis lawsoniana

As part of an on-going project to characterize compounds from immature conifer cones with antibacterial or modulatory activity against multidrug-resistant (MDR) strains of Staphylococcus aureus, eight compounds were isolated from the cones of Chamaecyparis lawsoniana. The active compounds were mainly diterpenes, with minimum inhibitory concentrations ranging from 4 to 128 microg/ml against MDR effluxing S. aureus strains and two epidemic methicillin-resistant (EMRSA) clinical isolates. The compounds extracted were the diterpenes ferruginol, pisiferol and its epimer 5-epipisiferol, formosanoxide, trans-communic acid and torulosal, the sesquiterpene oplopanonyl acetate and the germacrane 4beta-hydroxygermacra-1(10)-5-diene. Some of these compounds also exhibited modulatory activity in potentiating antibiotic activity against effluxing strains and ferruginol, used at a sub-inhibitory concentration, resulted in an 80-fold potentiation of oxacillin activity against strain EMRSA-15. An efflux inhibition assay using an S. aureus strain possessing the MDR NorA efflux pump resulted in 40% inhibition of ethidium bromide efflux at 10 microM ferruginol (2.86 microg/ml). We report the (1)H and (13)C NMR data for the cis A/B ring junction epimer of pisiferol which we have named 5-epipisiferol. We also unambiguously assign all (1)H and (13)C NMR resonances for trans-communic acid.     

Composition of the essential oil of the liverwort Radula perrottetii of Japanese origin

Analysis of the essential oil of the liverwort Radula perrottetii afforded two novel viscidane diterpenes, viscida-3,9,14-triene (1), viscida-3,11(18),14-triene (2), four bisabolane sesquiterpenes, bisabola-2,6,11-triene (3), bisabola-1,3,5,7(14),11-pentaene (4), bisabola-1,3,5,7,11-pentaene (5), 6,7-epoxybisabola-2,11-diene (6), and 1-methoxy-4-(2-methylpropenyl)benzene (7) as new natural products. In addition, the known compounds bisabola-1,3,5,7(14),10-pentaene (8), ar-tenuifolene (9), alpha-helmiscapene (10), and beta-helmiscapene (11) were also isolated. Isolation was carried out by preparative gas chromatography, and the structures were established by extensive NMR analysis. This is the first finding of viscidane diterpenes in liverworts. Compounds 8, 9 and the rarely encountered eudesmane sesquiterpene hydrocarbons 10 and 11 are reported for the first time from R. perrottetii.     

Insect-antifeedant and antibacterial activity of diterpenoids from species of Plectranthus

Bio-assay guided fractionation of an acetone extract of leaf material from Plectranthus saccatus Benth. resulted in the isolation of a beyerane diterpenoid. This compound, characterised by spectroscopic methods as ent-3beta-(3-methyl-2-butenoyl)oxy-15-beyeren-19-oic acid, showed insect antifeedant activity against Spodoptera littoralis. Known quinonoid abietane diterpenoids obtained from new sources included a mixture of the (4R,19R) and (4R,19S) diastereoisomers of coleon A from P. aff. puberulentus J.K. Morton, coleon A lactone from P. puberulentus J.K. Morton, and coleon U and coleon U quinone from P. forsteri 'Marginatus' Benth. These compounds, and the crude acetone extracts from the leaf surfaces of 11 species of Plectranthus, were tested for antifeedant activity against S. littoralis, antibacterial activity against Bacillus subtilis and Pseudomonas syringae and antifungal activity against Cladosporium herbarum. The coleon A mixture showed potent antifeedant activity against S. littoralis, whereas coleon U showed the greatest antimicrobial activity.     

Bioactive triterpene derivatives from latex of two Euphorbia species

We have investigated the antifeedant and toxic effects of 23 semisynthetic terpenoid derivatives obtained through chemical modifications of the major components of Euphorbia resinifera (alpha-euphol and alpha-euphorbol) and E. officinarum (obtusifoliol and 31-norlanostenol) latex on several insect species (Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi), their selective cytotoxicity on insect Sf9 and mammalian CHO cells and their phytotoxic effects on Lactuca sativa. The conversions focused mainly on positions 3,7,11, and 24 with several oxidizing agents. A total of 18 compounds affected S. littoralis growth (IGR). Our results support the importance of the C-3 substituent, suggest the involvement of the C-7 substituent and indicate that the C-3 hydroxyl is not essential for the IGR effect. Overall, Sf9 cells were more sensitive to the active compounds than CHO cells. All of these compounds had non selective moderate phytotoxic effects on radicle elongation of L. sativa.     

Trypanocidal activity of oleoresin and terpenoids isolated from Pinus oocarpa

Fractionation with n-hexane/ethyl acetate (1:1 v/v) by open column chromatography of the oleoresin from Pinus oocarpa Schiede yielded two diterpenes, pimaric acid (1) and dehydroabietic acid (5), the sesquiterpene longifolene (3) and a diterpenic mixture containing pimaric acid (1), isopimaric acid (4) and dehydroabietic acid (5). Subsequently, the isolated compounds, the mixture of 1, 4 and 5, the oleoresin and the dehydroabietic acid methyl ester (2), were tested in vitro against epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease. The most active compounds were 1, 3 and the oleoresin, being as active as nifurtimox, a drug effective in the treatment of acute infection by American trypanosomiasis and used in this work as positive control.     

A new ent-kaur-16-en-19-oic acid from the aerial parts of Inula bifrons

The phytochemical study of the chloroform extract of the aerial parts of Inula bifrons (L.) L. led to the isolation of one new ent-kaurane diterpenes acid along with twelve known compounds (two ent-kaurane diterpenoids, an eudesmane acid, five sesquiterpene lactones, three triterpenoids and β-sitosterol). All known compounds are found for the first time in I. bifrons. Their structures were elucidated by using spectral methods (NMR, HRESIMS and IR). The distribution of these compounds in the genus Inula and their chemotaxonomic significance is discussed.     

Diterpenes from the berries of Juniperus excelsa

From the hexane extract of berries of Juniperus excelsa, one new and four known diterpenes were isolated besides a known sesquiterpene. The structures of the known diterpenes were identified as isopimaric, isocommunic, (-)ent-trans communic and sandracopimaric acids, along with the sesquiterpene 4a-hydroxycedrol and the new compound which was elucidated as 3 alpha-acetoxylabda-8(17),13(16),14-trien-19-oic acid (juniperexcelsic acid). Cytotoxic activity of the hexane extract was investigated against a panel of cell line and found highly active against LNCaP, KB-V (+VLB) and KB-V (-VLB) cell lines. Furthermore, the hexane and methanol extracts, and the new compound were found to be moderately active against Mycobacterium tuberculosis.     

Insect antifeedant activity of clerodane diterpenes and related model compounds

A comprehensive compilation of all test results on the insect antifeedant activity of clerodane diterpenes and related model compounds is reported. To increase the compatibility of data from different sources, some of the results reported in the literature have been converted into a standardized form. The compounds were sorted into groups according to the different types of sidechain attached to C-9. Despite the wealth of information, collected in 15 tables, it remains difficult to assign importance to separate structural elements in relation to the observed antifeedant activity. A detailed analysis of the structure-activity relationships could not be presented, but some interesting trends can be distinguished based on the structures of the strongest antifeedants. The compilation covers the literature up to December 2001.     

Insect Antifeedants,Pterocarpans and Pterocarpol,in Heartwood of Pterocarpus macrocarpus Kruz.

The insect antifeedant activities of pterocarpans and a sesquiterpene alcohol from the dichloromethane extract of Pterocarpus macrocarpus Kruz. (Leguminosae) were evaluated against the common cutworm, Spodoptera litura F. (Noctuidae), and the subterranean termite, Reticulitermes speratus (Kolbe)(Rhinotermitidae). Three pterocarpans, (?)-homopterocarpin (1), (?)-pterocarpin (2), and (?)-hydroxyhomopterocarpin (3) and the sesquiterpene alcohol, (+)-pterocarpol (5), were isolated from the dichloromethane extract of the heartwood of P. macrocarpus under guidance by a biological assay. Among these natural products, the most active insect antifeedant against both S. litura and R. speratus was 1. On the other hand, sesquiterpene alcohol 5 showed less insect antifeedant activity than the other pterocarpans against both insect species. While its methylated derivative, (?)-methoxyhomopterocarpin (4), showed high biological activity, 3 showed less insect antifeedant activity in this study. Interestingly, racemic 1 did not show insect antifeedant activity against S. litura. However, all of the test pterocarpans and isoflavones showed antifeedant activity against the test termites. Additionally, since these compounds were major constituents of P. macrocarpus, these antifeedant phenolics may act as chemical defense factors in this tree. In Thailand, lumber made from this tree is used to make furniture and in building construction due to its resistance to termite attack.