The Implication of Short-Chain Fatty Acids in Obesity and Diabetes.

Evidence indicates that short-chain fatty acids (SCFAs) generated from the gut microbiota play crucial roles in host metabolism. They contribute to metabolic regulation and energy acquisition of the host by influencing the development of metabolic disorders. This review aims to synthesize recent advances from the literature to investigate the implication of SCFAs in the modulation of obesity and diabetes pathologies.

SAR study on Novel truxillic acid monoester-Based inhibitors of fatty acid binding proteins as Next-Generation antinociceptive agents.

Fatty acid binding protein 5 (FABP5) is a highly promising target for the development of analgesics as its inhibition is devoid of CBR-dependent side-effects. The design and discovery of highly potent and FABP5-selective truxillic acid (TA) monoesters (TAMEs) is the primary aim of the present study. On the basis of molecular docking analysis, ca.

Design, synthesis and SAR study of Fluorine-containing 3rd-generation taxoids.

It has been shown that the incorporation of fluorine or organofluorine groups into pharmaceutical and agricultural drugs often induces desirable pharmacological properties through unique protein-drug interactions involving fluorine. We have reported separately remarkable effects of the 2,2-difluorovinyl (DFV) group at the C3' position, as well as those of the CFO and CHFO groups at the 3-position of the C2-benzoyl moiety of the 2nd- and 3rd-generation taxoids on their potency and pharmacological properties. Thus, it was very natural for us to investigate the combination of these two modifications in the 3rd-generation taxoids and to find out whether these two modifications are cooperative at the binding site in the β-tubulin or not, as well as to see how these effects are reflected in the biological activities of the new 3rd-generation DFV-taxoids.

Structure and inhibition of Cryptococcus neoformans sterylglucosidase to develop antifungal agents.

Pathogenic fungi exhibit a heavy burden on medical care and new therapies are needed. Here, we develop the fungal specific enzyme sterylglucosidase 1 (Sgl1) as a therapeutic target. Sgl1 converts the immunomodulatory glycolipid ergosterol 3β-D-glucoside to ergosterol and glucose.

Potent antitumor activity of novel taxoids in anaplastic thyroid cancer.

Purpose: Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancers and it is rapidly fatal without any effective therapeutic regimens. There are some clinical trials showing that paclitaxel-based chemotherapy for ATC can achieve a relatively high response rate and low incidence of adverse reaction. The aim of this study was to evaluate potential therapeutic activity of novel taxoids in ATC cells.

A novel taxane, difluorovinyl-ortataxel, effectively overcomes paclitaxel-resistance in breast cancer cells.

Paclitaxel (PTX) is widely used to treat breast and ovarian cancers, but innate and acquired resistance often compromises its applications. The objective of this study was to screen new-generation taxanes for their efficiency against both PTX-sensitive and PTX-resistant breast cancer cells. From twelve compounds, difluorovinyl-ortataxel (DFV-OTX) displayed potent cytotoxic activities against both PTX-sensitive and PTX-resistant breast cancer cells.

Design, synthesis and SAR study of 3rd-generation taxoids bearing 3-CH, 3-CFO and 3-CHFO groups at the C2-benzoate position.

It has been shown that inclusion of CFO and CHFO groups to drug candidates often improve their pharmacological properties, especially metabolic stability, membrane permeability and PK profile. Moreover, the unique non-spherical structure of the OCHF group can provide interesting and beneficial characteristics. Accordingly, new 3rd-generation taxoids, bearing 3-OCF or 3-OCFH (and 3-CH for comparison) at the C2 benzoate moiety, were synthesized and their potencies against drug-sensitive and drug-resistant cancer cell lines examined.

Influence of pressure on ultrasonic cavitation activity in room temperature ionic liquids: An electrochemical study.

This paper provides proofs of the respective contributions of dissolved gases and solvent vapor on cavitation activity in sonoreactors. This activity can be detected by electrochemistry because the fluctuating events measured at the electrode surface are only linked to physical effects of cavitation. As ionic liquids present very low volatilities, their vaporization is reduced, and cavitation bubbles only depend on the presence of gases.