In vitro biological effects of two anti-diabetic medicinal plants used in Benin as folk medicine.

International audienceBACKGROUND: Extracts from Polygonum senegalensis (Polygonaceae) and Pseudocedrela kotschyi (Meliaceae) are two important traditionally used medicinal plants in rural Benin to treat many diseases and notably type 2 diabetes. The aim of the study was to investigate the alpha-glucosidase inhibition, antioxidant and antibacterial activities of those plants extract: Polygonum senegalensis leaves, and Pseudocedrela kotschyi root. METHODS: Hydro-alcoholic (50%) extracts were analyzed for their phytochemical content and tested for their inhibition potency on alpha-glucosidase from Saccharomyces cerevisiae. Antioxidant activities were assessed using the DPPH, ORAC, FRAP and DCFH-DA (cell based) assay. Finally, the antibacterial activity was evaluated using MIC determination on four Gram-positive cocci (Bacillus subtilis, Clostridium difficile, Enterococcus faecalis, Staphylococcus aureus), three Gram-negative bacilli (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae), and the yeast Candida albicans. RESULTS: Each extract presented significant alpha-glucosidase inhibition and antioxidant activities. Polygonum senegalensis leaf extracts were the most active in each in vitro assay with an IC50 = 1.5 mug/ml for alpha-glucosidase inhibition and an IC50 = 6.8 mug/ml for DPPH scavenging, - 4.5 mumol Fe II/g of dry matter - 9366 mumol Trolox / g DW - for FRAP and ORAC values, respectively. IC50 = 2.3 mug GA / ml for DCFH-DA assay. Concerning its antibacterial activity, a growth inhibitory effect was observed only against three Gram negative bacilli: B. subtilis, E. faecalis, S. aureus and the yeast C. albicans at high concentration. CONCLUSION: The results showed that the semi alcoholic extract of the two studied plants possess alpha-glucosidase inhibitory activity, antioxidant potency, and low antibacterial effect

Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins

International audienceThe synthesis of new meridianin derivatives substituted at the C-5 position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. These compounds were tested for their kinase inhibitory potencies toward five kinases (CDK5/p25, CK1δ/ε, GSK-3α/β, Dyrk1A and Erk2) as well as their in vitro antiproliferative activities toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 and PA 1

Synthesis and antiproliferative activities of indolin-2-one derivatives bearing amino acid moieties.

A convenient synthesis of indolin-2-ones substituted in the 3 position by an aminomethylene group bearing different amino acid moieties is described. Their antiproliferative activities were evaluated toward a panel of human solid tumor cell lines (PC 3, DLD-1, MCF-7, M4 Beu, A549, PA 1) and healthy cell lines (a murine fibroblast L929 and a human fibroblast primary culture

In vitro activity of hederacolchisid A1 compared with other saponins from Hedera colchica against proliferation of human carcinoma and melanoma cells

Hederacolchisid A1, a new oleanolic acid monodesmoside, isolated from Hedera colchica K. Koch, an ivy species endemic in Georgia, was evaluated in vitro for antiproliferative activity on cancer cells versus normal cells in comparison to cisplatin. Investigations were made on six human cell lines (colon adenocarcinoma DLD-1, ovarian teratocarcinoma PA 1, lung carcinoma A 549, breast adenocarcinoma MCFT, prostatic adenocarcinoma PC 3 and malignant melanoma M4 Beu) versus normal human fibroblasts, by assaying both cellular metabolic activity (RTT test) and DNA content in living cells (test with Hoechst 33342) after 48 h continuous contact. Results demonstrated the strong cytotoxicity of hederacolchisid A1 on all cancer cells (IC50 from 4.5 to 12 μM). The antiproliferative effects on malignant melanoma M4 Beu (IC50 ca 4.5 μM) versus normal cells (IC50 ca 7.5 μM) suggests that, despite a lack of specificity for cancer cells, hederacolchisid A1 has potential anti-tumor applications. Comparison of the cytotoxicity of hederacolchisid A1 with that of five other saponins from H. colchica, offers some new information about structure-activity relationships. It was observed that i) for a same sugar sequence, monodesmosides with oleanolic acid as aglycone exhibit higher cytotoxicity than those containing hederagenin, ii) the sugar sequence O-α-L-rhamnopyranosyl (1 → 2)-α-L-arabinopyranoside at C3 induces strong cytotoxicity and might be identified as a basic sequence for anti-tumor activity of oleanolic acid monodesmosides. iii) a complementary glucopyranosyl moiety branched at C1 of arabinose increases the cytotoxicity against malignant melanoma M4 Beu, prostatic adenocarcinoma PC 3 and normal fibroblasts in a different manner for each type of monodesmoside. A slight increase whose amplitude was quite similar on cancers and normal cells, was observed with oleanolic acid monodesmoside. This increase was much higher with hederagenin monodesmoside and markedly elevated in normal cells than in cancer cells

Synthesis and biological activities of pyrazolo[3,4-g]quinoxaline derivatives

International audienceThe synthesis of new pyrazolo[3,4-g]quinoxaline derivatives, as well as their Pim kinases (Pim-1, Pim-2, Pim-3) inhibitory potencies and in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145) are described. The results obtained in this preliminary structure–activity relationship study have pointed out that most of the compounds in this series exhibited interesting in vitro Pim-3 kinase inhibitory potencies. Moreover, some of the tested compounds have demonstrated favorable antiproliferative potencies

Total structure and inhibition of tumor cell proliferation of Laxa phycins

International audienc

Synthesis and biological evaluation of a new scaffold for Pim kinase inhibitors

Poste

Evaluation of biological effectiveness of 65 MeV therapeutic proton beams using the GATE platform

International audienceIntroduction: In order to optimize hadrontherapy treatments, it is needed to consider the biological effect on irradiated tumor cells. The biological dose can be evaluated through biophysical models, such as the Microdosimetric Kinetic Model (MKM)[1-5]. This model is implemented to take into account a corrected lineal energy spectrum obtained from Monte Carlo simulations and the model parameters of irradiated cells obtained from experiments. The purpose of this study is to validate the implementation of the MKM model into GATE through the simulation of the 65 MeV therapeutic proton beam (MediCyc) of Antoine Lacassagne centre for the estimation of the relative biological effectiveness (RBE)

Synthèse et activités biologiques des pyrazolo[3,4-g]quinoxalines

Communication oral

Synthesis and antiproliferative activities of indolin-2-one derivatives bearing amino-acid moieties

Poste