Synthetic Lethal Activity of Benzophenanthridine Alkaloids From Against BRCA1-Deficient Cancer Cells.

Several plants from South America show strong antitumoral properties based on anti-proliferative and/or pro-apoptotic activities. In this work we aimed to identify selective cytotoxic compounds that target BRCA1-deficient cancer cells by Synthetic Lethality (SL) induction. Using a high-throughput screening technology developed in our laboratory, we analyzed a collection of extracts from 46 native plant species from Argentina using a wide dose-response scheme.

Clinanthus microstephium, an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure-Activity Analysis of Haemanthamine Skeleton Derivatives.

Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR.

Semisynthesis and Inhibitory Effects of Solidagenone Derivatives on TLR-Mediated Inflammatory Responses.

A series of nine derivatives (⁻) were prepared from the diterpene solidagenone () and their structures were elucidated by means of spectroscopic studies. Their ability to inhibit inflammatory responses elicited in peritoneal macrophages by TLR ligands was investigated. Compounds and showed significant anti-inflammatory effects, as they inhibited the protein expression of nitric oxide synthase (NOS-2), cyclooxygenase-2 (COX-2), and cytokine production (TNF-α, IL-6, and IL-12) induced by the ligand of TLR4, lipopolysaccharide (LPS), acting at the transcriptional level.

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.

β-Agarofurans and Sesquiterpene Pyridine Alkaloids from Maytenus spinosa.

Nine new β-dihydroagarofurans (1-9) and four new sesquiterpene pyridine alkaloids (10-13) were isolated from the leaves of Maytenus spinosa. Their structures were determined mainly by 1D- and 2D-NMR spectroscopic studies. The absolute configuration of compound 6 was established using CD spectroscopy.

Antiproliferative and quinone reductase-inducing activities of withanolides derivatives.

Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity.

Synthesis and anti-HIV activity of lupane and olean-18-ene derivatives. Absolute configuration of 19,20-epoxylupanes by VCD.

Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra.

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.

Dihydro-β-agarofuran sesquiterpenoids from Plenckia integerrima.

Four new dihydroagarofurans (1-4) were isolated from the root bark of Plenckia integerrima. The structures of 1-4 were determined by means of 1D and 2D NMR techniques, and circular dichroism (CD) was used to determine the absolute configuration of compound 1.

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.

Pancratium canariense as an important source of amaryllidaceae alkaloids.

Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.

Withanolides from Jaborosa laciniata.

Six new trechonolide type withanolides (compounds 1- 6), together with trechonolide A, jaborotetrol, and 12- O-methyl jaborosotetrol, were isolated from the aerial parts of Jaborosa laciniata. The structures were elucidated on the basis of spectroscopic methods (1D and 2D NMR, MS).

Withanolides with phytotoxic activity from Jaborosa caulescens var. caulescens and J. caulescens var. bipinnatifida 1.

Seven new withanolides (1-7) were isolated from the aerial parts of Jaborosa caulescens var. caulescens and Jaborosa caulescens var. bipinnatifida.

Phytotoxic withanolides from Jaborosa rotacea.

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies.

15,21-Cyclowithanolides from Jaborosa bergii.

Six new withanolides (1-6) were isolated from the aerial parts of Jaborosa bergii plants and characterized by spectroscopic methods (1D and 2D NMR, MS). Five of the new compounds presented a novel norbornane-type structure in ring D of the steroid nucleus (1-5), resulting from a carbon-carbon bond between C-15 and C-21. The sixth withanolide isolated was the 5alpha-chloro-6beta-hydroxy analogue (6) of 2,3-dehydrojaborosalactol M (7), previously isolated from this plant.

Spiranoid withanolides from Jaborosa odonelliana.

Six new spiranoid withanolides, (20R,22R,23S)-5alpha-chloro-6beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (2), (20R,22R,23S)-5beta,6beta-epoxy-12beta,17beta,22-trihydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (3), (20R,22R,23S)-5beta,6beta-epoxy-4beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (4), (20R,22R,23S)-5alpha,6beta,12beta,17beta,22-pentahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (5), (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-5alpha-methoxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (6), and (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-2alpha,5alpha-epidioxy-1-oxo-12,23-cycloergosta-3,24-dien-26,23-olide (7), were isolated from the leaves of Jaborosa odonelliana. Compounds 2-7 were characterized by a combination of spectroscopic methods (1D and 2D NMR, MS) and molecular modeling.

Induction of quinone reductase by withanolides.

Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice.