Structural clarification of germacranolides from Calea species

The aerial parts of Calea pinnatifida contain a 4-glycosyloxybenzoic acid, anisic acid, tetradeca-4E,6E,12E-trien-8,10-diyn-1-ol and arucanolide. The structural elucidation of this germacranolide included comparison with neurolenin B whose stereochemistry had been defined by X-ray crystallographic analysis. The data suggest that the structures of all other known germacranolides of the genus Calea should be revised.     

The germacranolide sesquiterpene lactone neurolenin B of the medicinal plant Neurolaena lobata (L.) R.Br. ex Cass inhibits NPM/ALK-driven cell expansion and NF-κB-driven tumour intravasation

BackgroundThe t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata (L.) R.Br. ex Cass was shown to inhibit NPM/ALK expression.PurposeTherefore, we analysed whether the active principles that were recently isolated and found to inhibit inflammatory responses specifically inhibit growth of NPM/ALK+ ALCL, leukaemia and breast cancer cells, but not of normal cells, and the intravasation through the lymphendothelial barrier.MethodsALCL, leukaemia and breast cancer cells, and normal peripheral blood mononuclear cells (PBMCs) were treated with isolated sesquiterpene lactones and analysed for cell cycle progression, proliferation, mitochondrial activity, apoptosis, protein and mRNA expression, NF-κB and cytochrome P450 activity, 12(S)-HETE production and lymphendothelial intravasation.ResultsIn vitro treatment of ALCL by neurolenin B suppressed NPM/ALK, JunB and PDGF-Rβ expression, inhibited the growth of ALCL cells late in M phase, and induced apoptosis via caspase 3 without compromising mitochondrial activity (as a measure of general exogenic toxicity). Moreover, neurolenin B attenuated tumour spheroid intravasation probably through inhibition of NF-κB and CYP1A1.ConclusionNeurolenin B specifically decreased pro-carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF-kB signalling, attenuated tumour intra/extravasation into the lymphatics. Hence, neurolenin B may open new options to treat ALCL and to manage early metastatic processes to which no other therapies exist.     

Two guaianolides from calea solidaginea

The isolation and structure elucidation of two new guaianolides, solidaginolides A(1) and B(5), from Calea solidaginea are reported. The structures of the new compounds were established by spectroscopic methods.     

Germacranolides,calbertolides A,B and C,from Calea berteriana

The isolation and structure elucidation of two germacranolides, calbertolides A and B, and a heliangolide, calbertolide C, from Calea berteriana are reported. The structures of the new compounds were established by spectroscopic methods.     

Guaianolides from Calea subcordata

Chemical analysis of Calea subcordata yielded three new guaianolides, 8-epi-isobutyrylrupicolin A, 8-epi-isobutyrylrupicolin B and subcordatolide A, which represent the first guaianolide-type sesquiterpene lactones reported in the genus Calea. The structures of the new compounds were established by chemical and spectroscopic methods.     

Guaianolides and chromenes from Calea species

Chemical analysis of Calea berteriana yielded, besides the known flavonoid acacetin and the sesquiterpene lactone calbertolide C, three new guaianolides, desacyl-8-tiglylsubcordatolide A and 8-epi-8-tiglylrupicolins A and B. C. prunifolia provided acacetin, calbertolide C, desacyl-8-tiglylsubcordatolide A, and two new chromenes, prunichromenes A and B. From C. solidaginea acacetin, heliangine, calbertolide C, 8-epi-8-tiglylrupicolin A and desacyl-8-tiglylsubcordatolide A were isolated. The structures of the new compounds were established by chemical and spectral methods.     

Two sesquiterpene lactones of Calea ternifolia var. Calyculata

Chemical analysis of Calea ternifolia var. calyculata yielded the known sesquiterpene lactone calein A, as well as two new modified heliangolid     

Two furanoheliangolides from Calea angusta

Calea angusta afforded, in addition to known compounds, two new furanoheliangolides closely related to those of Calea pilosa.     

A heliangolide from Calea lantanoides

An extract of Calea lantanoides which inhibits larval development of Strongyloides stercoralis and three species of hookworms gave the heliangolide 15-deoxybudlein A.     

Further sesquiterpene lactones from Calea and Viguiera species

The aerial parts of Calea clematidea gave three new germacranolides, those of Viguiera procumbens two orizabin derivatives and those of V. linearis dihydrobudlein A. In addition to these lactones, several known ones were isolated.     

Eudesmanolides from Calea trichomata

Chemical analysis of Calea trichomata yielded, besides four known eudesmanolides, a new eudesmanolide, trichomatolide A. The structure of the new compound was established by chemical and spectral methods.     

A Taxonomic study of the calea orizabaensis complex and its bearing on the nomenclature of verbesina standleyi (Asteraceae)

Examination of type material ofVerbesina standleyi andCalea pachyphylla shows that the two taxa are conspecific. The older name,C. pachyphylla, has long been associated with the quite remote,C. orizabaensis. The latter is indistinguishable fromC. rupestris andC. guatemalensis; accordingly, these are placed in synonymy.Calea orizabaensis consists of two infraspecific taxa, var.orizabaensis and var.websteri; the latter is described as new.     

Calea dalyi (Compositae: Heliantheae), a new species from the Serranía de Santiago,Bolivia

A new species of Compositae, Calea dalyi (of section Meyeria), from eastern Bolivia is described and illustrated. Its closest congener is C. purpurea from westernmost Bahia, Brazil. A key to the members of the C. teucriifolia complex is provided.     

Heliangolides,and nerolidol and p-hydroxyacetophenone derivatives from Calea species

A new Calea species afforded a heliangolide, closely related to niveusin C, while from Calea teucrifolia two new nerolidol derivatives and eight p-hydroxyacetophenone derivatives were isolated. The structures were elucidated by spectroscopic methods and a few chemical transformations. The spectral data of 8β-angeloylatripliciolide, the main constituent of C. teucrifolia, are also included. The chemotaxonomic situation is discussed briefly.     

Germacranolides related to chapliatrin from calea harleyi

The roots of Calea harleyi afforded four germacranolides closely related to chapliatrin and two derivatives of p-hydroxyacetophenone related to the acyloxycalefoliones.     

Reduced acetophenone derivatives from Calea cuneifolia

Six reduced p-hydroxyacetophenones, a p- hydroxyvinylbenzene derivative, a chromanone, and acetylsarracinic acid were isolated from the xylopodium of Calea cuneifolia. The constitutions were elucidated by spectroscopic methods and a few chemical transformations.     

Sesquiterpene lactones from Calea leptocephala

Chemical analysis of Calea leptocephala yielded seven sesquiterpene lactones three of which had not been previously reported as natural products. The new compounds were represented by a furanoheliangolide, 8β-angeloyloxy-9α-acetoxycalyculatolide, the germacranolide desacetylcalein A, and a guaianolide, 8β-angeloyloxyleptocephalide. The structures of the new compounds were established by spectroscopic methods.     

Three furanoheliangolides from Calea villosa

Calea villosa afforded three new sesquiterpene lactones, two furanoheliangolides and an epoxy- germacranolide, as well as several known compounds. The structures were elucidated by spectroscopic methods.     

Furanoheliangolides and farnesol derivatives from Calea hispida

From Calea hispida, in addition to known compounds, two new furanoheliangolides, one substituted with a myrtenyl residue, two further farnesol deri     

Eudesmanolides and heliangolides from Calea rotundifolia

The aerial parts of Calea rotundifolia afforded, in addition to known compounds, heliangin and two further closely related lactones as well as three new eudesmanolides and a norterpene ketone. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly.