Selective Antiproliferative Withanolides from Species in the Genera Eriolarynx and Deprea.

Four new withanolides (2-5), together with 4ß,7ß,20-trihydroxy-1-oxowitha-2,5,24-trienolide (1), were isolated from the aerial parts of Eriolarynx iochromoides. The antiproliferative activity of all compounds purified from E. iochromoides together with four withaphysalins and four physangulidines isolated previously from three Deprea species were evaluated against human solid tumor cell lines. Four withanolides showed antiproliferative activity comparable in potency to cisplatin. Selectivity toward cancer cells and interaction with P-glycoprotein of the active withanolides were evaluated.

Structure and antimicrobial activity of phloroglucinol derivatives from Achyrocline satureioides.

The new prenylated phloroglucinol α-pyrones 1-3 and the new dibenzofuran 4, together with the known 23-methyl-6-O-demethylauricepyrone (5), achyrofuran (6), and 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphaliin A), were isolated from the aerial parts of Achyrocline satureioides. Their structures were determined by 1D and 2D NMR spectroscopic studies, while the absolute configuration of the sole stereogenic center of 1 was established by vibrational circular dichroism measurements in comparison to density functional theory calculated data. The same (S) absolute configuration of the α-methylbutyryl chain attached to the phloroglucinol nucleus was assumed for compounds 2-6 based on biogenetic considerations. Derivatives 7-16 were prepared from 1 and 5, and the antimicrobial activities of the isolated metabolites and some of the semisynthetic derivatives against a selected panel of Gram-positive and Gram-negative bacteria, as well as a set of yeast molds, were determined.

Antibacterial activity of withanolides and their structure-activity relationship.

Two new withanolides, (17R,20S,22R)-4ß-acetoxy-5ß,6ß-epoxy-19,27-dihydroxy-1-oxo-witha-2,24-dienolide (withalongolide A 4-acetate (5) and (17R,20S,22R)-5ß,6ß-epoxy-27-hydroxy-1,4-dioxo-witha-24-enolide (9), and seven known withanolides with normal structure (1-4, 6-8) were isolated from aerial parts of Cuatresia colombiana. Several semisynthetic derivatives were prepared from the natural metabolites withaferin A and jaborosalactone 38. The compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The compounds isolated from C. colombiana, sixteen withanolides previously isolated from different Solanaceae species with different skeletons and semisynthetic derivatives were evaluated for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. According to the bioactivity against S. aureus and E. faecalis, the compounds evaluated were divided into three groups: compounds with high activity (MIC 0.063 mM), compounds with moderate activity (0.5 mM > MIC > 0.125 mM) and non-active compounds (MIC ≥1 mM); in addition, some structure-activity relationship keys could be inferred.

Quest for antibacterial alkaloids from Rauhia multiflora through bioassay complementary-guided fractionation.

The clinical efficacy of many existing antibiotics is currently threatened by the emergence of microbial resistance. This recognized worldwide situation prompts to greater efforts to discover antimicrobial agents of natural origin, including plant sources. The objective of this work was to evaluate the antimicrobial activities of extracts, fractions and pure compounds from Rauhia multiflora using a bioguided complementary fractionation, contributing also to explain some traditional uses of this genus. Some subfractions showed antimicrobial activity against the Gram-negative and Gram-positive bacteria. Galantamine was identified and isolated as the main alkaloid, together with two additional structures of the same skeleton. Characterization by GC-MS revealed the presence of twelve galantamine-type and four crinane-type compounds. The tentative structure of one of the galantamine-type skeletons is proposed here for the first time. Altogether, these results support the use of Rauhia genus to inhibit bacterial growth.

Antioxidant characteristics and antibacterial activity of native woody species from Catamarca, Argentina.

Numerous reports describe the antioxidant and antimicrobial activity of polyphenols-rich plant extracts. The aim of this study was to determine the total polyphenols content (TPC), and the in vitro (DPPH, FRAP and TEAC) antioxidant and antibacterial activity of leaves and wood of six native woody species (Aspidosperma quebracho-blanct, Sarcomphalus mistol, Geoffroea decorticans, Prosopis chilensis, Larrea divaricata and Larrea cuneifolia) from Catamarca. Also, the phenolic profile was determined in the species with higher activity. L. cuneifolia leaf extracts showed the highest antioxidant activity followed by L. divaricata and S. mistol, while S. mistol wood extracts showed the highest. Furthermore, Larrea species showed antibacterial activity against S. aureus and E. faecalis strains showing cidal effects mainly against S. aureus. Fifty-nine polyphenols were identified in leaves and wood of Larrea and S. mistol species, which are likely to be responsible for the different activities observed.

Withanolides from the genus Exodeconus (Solanaceae). Chemotaxonomical considerations.

Five Exodeconus species were phytochemically analyzed. From the aerial parts of E. pusillus, the 7α,27-dihydroxy-1-oxo-22R-witha-2,5,24-trienolide and three other previously unreported normal-type withanolides were isolated. All the studied species had normal type and/or ring-D aromatic withanolides, and some had already been isolated from other Solanaceae genera, and therefore, these compounds are not chemotaxonomic markers at the generic level. The chemical composition of an undescribed Exodeconus species analyzed here supports the designation of this taxon as a new entity. The integral chemical profile of Exodeconus can be evaluated for its taxonomic implication when a more robust phylogeny of Solanaceae is available that allows the phylogenetic relationships with its closest genera to be clarified.

Withanolides from three species of the genus Deprea (Solanaceae). Chemotaxonomical considerations.

Nine withanolides were isolated from the aerial parts of Deprea bitteriana, Depreacuyacensis, and Depreazamorae. D.bitteriana yielded two withaphysalins, D. cuyacensis gave two 13,14-seco withaphysalins, while D. zamorae yielded five physangulidines. The compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). All compounds isolated from D.bitteriana and D. cuyacensis were obtained as epimeric mixtures at C-18. The structure of physangulidine D was confirmed by X-ray diffraction analysis. The skeletons found in this research support the chemotaxonomical position of the genus Deprea in the tribe Physalideae.

Achyrofuran is an antibacterial agent capable of killing methicillin-resistant vancomycin-intermediate Staphylococcus aureus in the nanomolar range.

Currently, there is a pressing need for novel antibacterial agents against drug-resistant bacteria, especially those which have been common in our communities and hospitals, such as methicillin-resistant Staphylococcus aureus (MRSA). The South American plant Achyrocline satureioides ("Marcela") has been widely used in traditional medicine for a number of diseases, including infections. Several crude extracts from this plant have shown good antimicrobial activities in vitro. In the search for the active principle(s) that confers these antimicrobial activities, we have processed the dichloromethane extract from the aerial parts of the plant. One of the isolated compounds showed extraordinary antibacterial activities against a set of clinically relevant Gram-positive strains that widely differ in their antibiogram profiles. This compound was identified as achyrofuran on the basis of its spectroscopic and physical data. We determined the MIC to be around 0.1 µM (0.07 µg/ml) for the reference methicillin-resistant and vancomycin-intermediate S. aureus strain NRS402. Moreover, nanomolar concentrations of achyrofuran killed 10(6) bacteria within 12 h. Based on the presence of the 2,2'-biphenol core, we further studied whether achyrofuran killed bacteria through a mechanism of action similar to that reported for the naturally occurring antibiotic MC21-A. Indeed, we found that achyrofuran was not bacteriolytic by itself although it greatly compromised membrane impermeability as determined by increased SYTOX Green uptake.