Viviana E. Nicotra

Withanolides and Related Steroids

Since the isolation of the first withanolides in the mid-1960s, over 600 new members of this group of compounds have been described, with most from genera of the plant family Solanaceae. The basic structure of withaferin A, a C28 ergostane with a modified side chain forming a δ-lactone between carbons 22 and 26, was considered for many years the basic template for the withanolides. Nowadays, a considerable number of related structures are also considered part of the withanolide class; among them are those containing γ-lactones in the side chain that have come to be at least as common as the δ-lactones. The reduced versions (γ and δ-lactols) are also known. Further structural variations include modified skeletons (including C27 compounds), aromatic rings and additional rings, which may coexist in a single plant species. Seasonal and geographical variations have also been described in the concentration levels and types of withanolides that may occur, especially in the Jaborosa and Salpichroa genera, and biogenetic relationships among those withanolides may be inferred from the structural variations detected. Withania is the parent genus of the withanolides and a special section is devoted to the new structures isolated from species in this genus. Following this, all other new structures are grouped by structural types.

Stereochemistry Determination by Powder X‐Ray Diffraction Analysis and NMR Spectroscopy Residual Dipolar Couplings

A matter of technique: For a new steroidal lactol, jaborosalactol 24 (1), isolated from Jaborosa parviflora, NMR spectroscopy residual dipolar couplings and powder X-ray diffraction analysis independently gave the same stereochemistry at C23-C26. Conventional NMR spectroscopic techniques, such as NOE and {sup 3}J coupling-constant analysis failed to unambiguously determine this stereochemistry.

Antiproliferative activity of withanolides against human breast cancer cell lines.

The in vitro antiproliferative activity of a series of 22 naturally occurring withanolides was examined against the T-47D, MCF7, MCF7/BUS, MDA-MB-231, and SK-Br-3 human solid tumor breast cancer cell lines. The most active compound showed GI(50) values in the range 0.16-0.71 muM. The aromatic withanolide 19 exhibited specific activity for the estrogen-receptor-positive cell lines (T-47D, MCF7, and MCF7/BUS). Overall, the results demonstrated the relevance of the substitution pattern on the A and B rings on the resultant antiproliferative activity.

Antiproliferative activity of withanolide derivatives from Jaborosa cabrerae and Jaborosa reflexa. Chemotaxonomic considerations.

Three withanolides were isolated from the aerial parts of Jaborosa reflexa Phil. Jaborosa cabrerae Barboza yielded five sativolide withanolides (including jaborosalactones R, S, 38, and 39) and two trechonolide withanolides epimeric at C-23 (trechonolide A and jaborosalactone 32). In addition, five derivatives were obtained by chemical derivatization of jaborosalactone 38, and all compounds were fully characterized by 1D and 2D NMR spectroscopic studies. The in vitro antiproliferative activities of the major natural withanolides and the semisynthetic derivatives were examined against HBL-100, HeLa, SW1573, T-47D, and WiDr human solid tumor cancer cell lines. Some chemotaxonomic considerations are discussed.

Withanolides with Antibacterial Activity from Nicandra john-tyleriana

Eleven new withanolides (1-11) were isolated and characterized from the aerial parts of Nicandra john-tyleriana. Five of these withanolides have an unmodified skeleton (1-5), two are acnistins (6, 7), and four are withajardins (8-11). These new isolates were fully characterized using a combination of spectroscopic techniques (including multidimensional NMR) and mass spectrometry. All compounds were evaluated for their antibacterial activity against Bacillus, Enterococcus, Escherichia, Listeria, Pseudomonas, and Staphylococcus strains.

Withanolides with Phytotoxic Activity from Two Species of the Genus Salpichroa: S. origanifolia and S. tristis var. lehmannii

Seven new withanolides, salpichrolides O-U (1-7), the known 2,3-dihydrosalpichrolide B (9), a substance not previously isolated from a natural source, and three known compounds, salpichrolide D (8), salpichrolide A (10), and salpichrolide C (11), were isolated and characterized from the aerial parts of Salpichroa origanifolia and S. tristis var. lehmannii. Compounds 1-4 and 8 have an oxygenated D ring, while compounds 5-7 and 9-11 possess a six-membered aromatic D ring. The structures of the isolated compounds were identified by analysis of their spectroscopic data including NMR and MS. Withanolides 1, 3, 8, 10, and 11 exhibited selective radicle growth inhibition toward Lactuca sativa (lettuce) at 150 and 400 ppm.

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.

Reaction of 2,4-Dinitrochlorobenzene with Aromatic Amines in Toluene: Effect of Nucleophile Structure

The kinetics of the reaction of 2,4-dinitrochlorobenzene (DNClB) with aniline and substituted anilines such as p-anisidine, p-toluidine and N-methylaniline have been studied in toluene. Except for N-methylaniline the reactions have shown a third order in amine rate dependence which is consistent with aggregates of the amine acting as the nucleophile. On the other hand, the reaction of DNClB with N-methylaniline under the same conditions shows a linear dependence of the second order rate coefficient, kA, vs [amine], which is consistent with the previous mechanism.

New Withanolides from Two Varieties of Jaborosa Caulescens

The phytochemical study of two species of Jaborosa caulescens (var. caulescens and var. bipinnatifida) yielded the four new withanolides 1-4. The structures of the new compounds were determined using a combination of spectroscopic techniques (including 1D and 2D NMR) and Molecular Modeling.

Agarofuran sesquiterpenes from Schaefferia argentinensis

Sixteen dihydro-β-agarofuran sesquiterpenes were isolated from the aerial parts of Schaefferia argentinensis Speg. Their structures were determined by a combination of 1D and 2D NMR and MS techniques. The in vitro antiproliferative activity of the major sesquiterpenes was examined in T47D, MCF7, and MDA-MB231 human cancer cell lines, but was found to be marginal.