Liver cancer antiproliferative activity of a new nor-cucurbitacin from Mareya micrantha Müll. Arg.

Mareya micrantha Müll. Arg. (Euphorbiaceae) is a plant used in the Ivorian traditional medicinal system for various medical properties such as laxative, oxytocic, intestinal infectious diseases, malaria, etc.

Potent Antiplasmodial Derivatives of Dextromethorphan Reveal the -Morphinan Pharmacophore of Tazopsine-Type Alkaloids.

The alkaloid tazopsine was introduced in the late 2000s as a novel antiplasmodial hit compound active against hepatic stages, with the potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) , although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, precluding its direct repurposing against the disease.

Countrywide Survey of Plants Used for Liver Disease Management by Traditional Healers in Burkina Faso.

Liver disease is highly prevalent in Africa, especially in the western African country Burkina Faso, due to the presence of multiple biological and chemical aggressors of the liver. Furthermore, diagnosis and appropriate care for liver disease are uneven and usually insufficient. This drives local communities to turn to folk medicine based on medicinal plants from healers.

Triterpenoid saponins from Calliandra calothyrsus Meisn. and their antiproliferative activity against two digestive carcinoma human cell lines.

The chemical investigation of the flowers and twigs of Calliandra calothyrsus (Fabaceae) led to the isolation of three new oleanane-type triterpenoid saponins, named calothyrsusosides AC (13). Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR and 2D NMR (H, H NMR DOSY, C NMR, COSY, HSQC, HMBC, HSQC-TOCSY and NOESY) and by comparison with literature data. Compounds 1 and 2 were tested for their antiproliferative activity against two digestive carcinoma human cell lines: Hep3B (hepatocellular carcinoma) and Caco-2 (epithelial colorectal adenocarcinoma).

Phenolic Compounds Isolated from Caesalpinia coriaria Induce S and G2/M Phase Cell Cycle Arrest Differentially and Trigger Cell Death by Interfering with Microtubule Dynamics in Cancer Cell Lines.

(), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim of this study was to isolate and identify the active compounds of a water:acetone:ethanol (WAE) extract of pods and characterize their cytotoxic effect and cell death induction in different cancer cell lines.

MSK1 triggers the expression of the INK4AB/ARF locus in oncogene-induced senescence.

The tumor suppressor proteins p15(INK4B), p16(INK4A), and p14(ARF), encoded by the INK4AB/ARF locus, are crucial regulators of cellular senescence. The locus is epigenetically silenced by the repressive Polycomb complexes in growing cells but is activated in response to oncogenic stress. Here we show that the mitogen- and stress-activated kinase (MSK1) is up-regulated after RAF1 oncogenic stress and that the phosphorylated (activated) form of MSK1 is significantly increased in the nucleus and recruited to the INK4AB/ARF locus.

Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells.

Ethnopharmacological Relevance: The high incidence of human hepatocellular carcinoma (HCC) in Peru and the wide use of medicinal plants in this country led us to study the activity against HCC cells in vitro of somes species used locally against liver and digestive disorders.

Materials And Methods: Ethnopharmacological survey: Medicinal plant species with a strong convergence of use for liver and digestive diseases were collected fresh in the wild or on markets, in two places of Peru: Chiclayo (Lambayeque department, Chiclayo province) and Huaraz (Ancash department, Huaraz province). Altogether 51 species were collected and 61 ethanol extracts were prepared to be tested.

Synthesis, structures, and selective toxicity to cancer cells of gold(I) complexes involving N-heterocyclic carbene ligands.

New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3.

Estrogen receptor α/β-cofactor motif interactions; interplay of tyrosine 537/488 phosphorylation and LXXLL motifs.

The Estrogen Receptors ERα and ERβ bind cofactor proteins via short LXXLL motifs. The exact regulation and selectivity of these interactions remains an open question and the role of post-translational modifications (PTMs) is virtually unexplored. Here, we designed an X(7)-LXXLL-X(7) T7 phage display library and screened this against four ER protein constructs: the 'naked' ERα and ERβ Ligand Binding Domains (LBDs) and the tyrosine phosphorylated ERα (pY537) and ERβ (pY488) LBDs.

Perturbation of estrogen receptor alpha localization with synthetic nona-arginine LXXLL-peptide coactivator binding inhibitors.

The interaction of estrogen receptor alpha (ERalpha) with the consensus LXXLL motifs of transcriptional coactivators provides an entry for functional ERalpha inhibition. Here, synthetic cell-permeable LXXLL peptide probes are brought forward that allow evaluation of the interaction of specific recognition motifs with ERalpha in the context of the cell. The probes feature a nona-arginine tag that facilitates cellular entry and induces probe localization in nucleoli.

Isolation and antimalarial activity of new morphinan alkaloids on Plasmodium yoelii liver stage.

Decoction of Strychnopsis thouarsii is used in the Malagasy traditional medicine to combat malaria. We have shown that this traditional remedy prevents malaria infection by targeting Plasmodium at its early liver stage. Bioassay-guided fractionation of S.

A plant-derived morphinan as a novel lead compound active against malaria liver stages.

Background: The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s.

Methods And Findings: Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar.

Design and synthesis of novel imidazo[1,2-a]quinoxalines as PDE4 inhibitors.

New imidazo[1,2-a]quinoxaline derivatives have been synthesised by condensation of an appropriate alpha-aminoalcohol with a quinoxaline followed by intramolecular cyclisation and nucleophilic substitutions. Their phosphodiesterase inhibitory activities have been assessed on a preparation of the PDE4 isoform purified from a human alveolar epithelial cell line (A549). These studies showed potent inhibitory properties that emphasize the importance of a methyl amino group at position 4 and a weakly hindered group at position 1.