Aurelio San-Martín

Diterpenoids from Azorella yareta and their trichomonicidal activities

Diterpenoids with trichomonicidal activity were isolated from the aerial parts of Azorella yareta Hauman. One was 13beta-hydroxyazorellane, together with the known constituents mulinolic acid, mulin-11,13-dien-20-oic acid, azorellanol and 13alpha-hydroxyazorellane. Their structures were determined by spectroscopic and chemical methods.

Isoepitaondiol, a diterpenoid of Stypopodium flabelliforme and the insecticidal activity of stypotriol, epitaondiol and derivatives

Abstract A new diterpenoid of mixed biogenesis; isoepitaondiol, has been isolated together with known diterpenoids and two chromones from the alga Stypopodium flabelliforme collected at Easter Island.

Stereostructure reassignment and absolute configuration of isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme.

Careful examination of the published NMR data for isoepitaondiol, a meroditerpenoid from Stypopodium flabelliforme, suggests that its published structure 1 must be revised. On the basis of extensive 1D and 2D NMR studies, we now propose that structure 2, with a trans-anti-trans-anti-cis arrangement fits isoepitaondiol diacetate. The relative configuration of 2 was confirmed by single-crystal X-ray diffraction, while the absolute configuration was evidenced by vibrational circular dichroism in combination with DFT B3LYP/DGDZVP calculations.

Pharmaco-toxicological study of diterpenoids

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.

Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids.

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-alpha-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 microg/mL against both strains. The methylated derivatives 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13), mulin-11,13-dien-20-oic acid methyl ester (15) and mulinenic acid methyl ester (23) proved to be more active than the parent compounds.

Insecticide and acaricide activities of polyhalogenated monoterpenes from chilean Plocamium cartilagineum

Abstract Four new alicyclic monoterpenes based on the 1-(2-chlorovinyl)-2,4,5-trichloro-1,5-dimethylcyclohexane skeleton were isolated from Plocamium cartilagineum from the Chilean coast, together with four known cyclic monoterpenes. The structure of the new compounds were determined by comparison of the spectral data with those of known compounds. The insecticide/acaricide and fungicide activities of some of the isolated monoterpenes were determined.

Tropane alkaloids from Schizanthus grahamii

Abstract Three new tropanol dimers of mesaconic and itaconic acids and 3α-senecioyloxytropane, together with other known alkaloids, were isolated from Schizanthus grahamii . The structures of the new compounds were established by spectroscopic and chemical transformations including 2-D long-range 13 C- 1 H correlations.

11,12-EPOXY-MULIN-13-EN-20-OIC acid, a diterpenoid from azorella compacta

A new diterpenoid, 11,12-epoxy-mulin-13-en-20-oic acid, was isolated from the aerial parts of Azorella compacta Phil. (Umbelliferae). Its structure determination was based on spectroscopic comparison with isomulinic acid.

Cytotoxic Activity of Halogenated Monoterpenes from Plocamium cartilagineum

Nine halogenated monoterpenes isolated from the red alga Plocamium cartilagineum have been evaluated for their cytotoxic effects on the tumor cell lines CT26 (murine colon adenocarcinoma), SW480 (human colon adenocarcinoma), HeLa (human cervical adenocarcinoma) and SkMel28 (human malignant melanoma) with several multidrug resistance mechanisms and the mammalian non-tumor cell line CHO (Chinese hamster ovary cells). The activities of these compounds were compared with those of the insecticide γ-hexachlorocyclohexane (lindane) due to chemical structure similarities. Compounds 1, 2, 3, and 5 exhibited selective cytotoxicity against colon and cervical adenocarcinoma cells. Interestingly, the effect of compound 3 was specific and irreversible to human colon adenocarcinoma SW480 cells, which overexpress the transmembrane P-glycoprotein often related to chemoresistance. None of the anti-tumor doses of these compounds was cytotoxic against CHO cells. Furthermore, analysis of cellular extracts after incubation with the test compounds and rotenone (positive uptake control) demonstrated the intracellular accumulation of 1, 2, 3, and 5.

NEW BUTYROLACTONE FROM A MARINE-DERIVED FUNGUS ASPERGILLUS SP

Four compounds that belong to two structure types, namely dibenzylbutyrolactone and sesterterpenoids, were obtained from the extract of the strain Aspergillus sp. (2P-22), isolated from a marine sponge, Cliona chilensis. Among them, compound 1 was identified as new, namely butylrolactone-VI. The structures of these compounds were characterized on the basis of spectroscopic data. Biological activities of these fungal metabolites, are described.