Enhancing structural diversity through chemical engineering of Ambrosia tenuifolia extract for novel anti-glioblastoma compounds.

Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for modifying complex natural products, leading to analogs that are unattainable by chemical semisynthesis or total synthesis. In this report, through the combination of natural products chemistry and diversity-oriented synthesis, a diversity-enhanced extracts approach is proposed using chemical reactions that remodel molecular scaffolds directly on extracts of natural resources.

Expanding Diterpene Complexity and Diversity via Photoinduced Ring Distortions.

Natural products and their semi-synthetic derivatives undoubtedly constitute an important source of therapeutic agents. Their importance lies in their own origin and evolution, since they have great chemical diversity, biochemical specificity, and pharmacological properties. Currently, there is a renewed interest in the development of methodologies capable of efficiently modifying the chemical structure of these bioactive platforms.

Antibacterial activity of withanolides and their structure-activity relationship.

Two new withanolides, (17R,20S,22R)-4β-acetoxy-5β,6β-epoxy-19,27-dihydroxy-1-oxo-witha-2,24-dienolide (withalongolide A 4-acetate (5) and (17R,20S,22R)-5β,6β-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).

Quest for antibacterial alkaloids from 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 using a bioguided complementary fractionation, contributing also to explain some traditional uses of this genus.

Identification of potential biological target for trypanocidal sesquiterpene lactones derivatives.

Sesquiterpene lactones are natural products of the Asteraceae family that have shown trypanocidal activity against , even exceeding the effectiveness of drugs used in the treatment of American trypanosomiasis. However, there is no agreement on their mechanism of action and their specificity to interact with parasite proteins. For this reason, we aimed to find biological targets that can interact with these compounds by reverse virtual screening with ligand pharmacophores and putative binding sites and the use of bioinformatic databases.

Identification of chia, flax and sesame seeds authenticity markers by NMR-based untargeted metabolomics and their validation in bakery products containing them.

Chia, flax, and sesame seeds are considered superseeds due to their beneficial nutritional properties, and they are frequently included as functional ingredients in foods. Authenticity markers of these seeds, including bakery products containing them, have been identified by both liquid and gas chromatography coupled to mass spectrometry (LC-MS/MS and GC-MS/MS, respectively) targeted metabolomics. However, there are no reports describing the use of nuclear magnetic resonance (NMR) spectroscopy based metabolomics to identify authenticity markers in either the raw seeds or foods containing them.

Psilostachyins as trypanocidal compounds: Bioguided fractionation of Ambrosia tenuifolia chemically modified extract.

This work focusses on the chemical diversification of an Ambrosia tenuifolia extract and its bioguided fractionation, aiming to unveil the chemical entity responsible for the trypanocidal activity. Besides, a revision of the phytochemical study of this species, based on previous reports of the antiparasitic psilostachyins A and C as main compounds, was conducted. To improve the biological properties of a plant extract through a simple chemical reaction, the oxidative diversification of the dichloromethane extract of this plant species was carried out.

Design, synthesis and evaluation of cholinesterase hybrid inhibitors using a natural steroidal alkaloid as precursor.

To date, Alzheimer's disease is the most alarming neurodegenerative disorder worldwide. This illness is multifactorial in nature and cholinesterase inhibitors have been the ones used in clinical treatments. In this context, many of these drugs selectively inhibit the acetylcholinesterase enzyme interacting in both the active site and the peripheric anionic site.

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.

An activity prediction model for steroidal and triterpenoidal inhibitors of Acetylcholinesterase enzyme.

Nowadays, the importance of computational methods in the design of therapeutic agents in a more efficient way is indisputable. Particularly, these methods have been important in the design of novel acetylcholinesterase enzyme inhibitors related to Alzheimer's disease. In this sense, in this report a computational model of linear prediction of acetylcholinesterase inhibitory activity of steroids and triterpenes is presented.

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.

Phytochemical Study of Senecio volckmannii Assisted by CASE-3D with Residual Dipolar Couplings and Isotropic H/C NMR Chemical Shifts.

Nine new eremophilanolides, with seven known sesquiterpenoids, and 4-hydroxyacetophenone were isolated from the aerial parts of Senecio volckmannii var. volckmannii. The structures of these compounds were fully characterized using a combination of spectroscopic techniques including multinuclear and multidimensional NMR and mass spectrometry.

Di(ethylene glycol) methyl ether methacrylate (DEGMEMA)-derived gels align small organic molecules in methanol.

Residual dipolar couplings (RDCs) constitute an important NMR parameter for structural elucidation in all areas of chemistry. In this study, di(ethylene glycol) methyl ether methacrylate (DEGMEMA)-based gels are introduced as alignment media for the measurement of RDCs of small organic molecules in polar solvents such as methanol. The low viscosity of methanol permits the execution of J-scaled BIRD HSQC experiments that yield very sharp lines in anisotropic conditions.

Solanocapsine derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies.

The investigation of natural products in medicinal chemistry is essential today. In this context, acetylcholinesterase (AChE) inhibitors comprise one type of the compounds most actively studied in the search for an effective treatment of symptoms of Alzheimer's disease. This work describes the isolation of a natural compound, solanocapsine, the preparation of its chemical derivatives, the evaluation of AChE inhibitory activity, and the structure-activity analysis of relevant cases.

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.

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.

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.