The Bioactive Phenolic Agents Diaryl Ether CVB2-61 and Diarylheptanoid CVB4-57 as Connexin Hemichannel Blockers

Inflammation mediators enhance the activity of connexin (Cx) hemichannels, especially in the epithelial and endothelial tissues. As potential release routes for injury signals, such as (oligo)nucleotides, Cx hemichannels may contribute to long-lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long-lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells, using dye uptake as functional assay. Moreover, the possible impacts of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (>5 µM) and Cx46 (>20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversibly inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to the stimulation of adenosine signalling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversibly block Cx hemichannels. Deciphering the mechanisms of the interactions of these agents with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for better and safer treatment of pathologies that involve Cx hemichannels

Synthesis of phosphonocinnamic thioesters, substrate analogues of cinnamoyl-CoA reductase, a key enzyme in the lignification process

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New Acyclic β-Functionnalized (E) Allyl Alcohols and their Bromomethyldimethylsilyl Ethers as Cyclopentanoids Precursors

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Regio- and stereospecificity in radical cascade cyclizations of TMS-alcyne containing allyl bromomethyldimethylsilyl ethers

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Sequential radical cyclization of β-functionalized allyl bromomethyldimethylsilyl ethers. Application to the regio- and stereo-specific synthesis of an isoprostanoid precursor

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Anti-inflammatory Activity of Naturally Occuring Diarylheptanoids - A Review

International audienceInflammation involving the innate and adaptive immune systems is a normal response to infection. However, if it becomes uncontrolled, inflammation may result in autoimmune or auto inflammatory disorders, neurodegenerative diseases or cancers. The currently available anti-inflammatory drug therapy is often not successful or induces severe side effects. Thus, the search of new therapeutic options for the treatment of inflammation is highly required. Medicinal plants have been an interesting source for obtaining new active compounds. Diarylheptanoids characterized by a 1, 7-diphenylheptane structural skeleton, are a class of secondary plant metabolites that have gained increasing interest over the last few decades due to a wide variety of biological activities. This review covers 182 natural linear or macrocyclic diarylheptanoids described in the period of 1982 to 2020 with anti-inflammatory activities evaluated using quantified in vitro and/or in vivo assays. All of these data highlight the pharmacological potential of these natural compounds to act as anti-inflammatory drugs

Cinnamic Acid Derivatives as Anticancer Agents-A Review

International audienceCinnamic acid and its phenolic analogues are natural substances. Chemically, in cinnamic acids the 3-phenyl acrylic acid functionality offers three main reactive sites; substitution at the phenyl ring, addition at the α,β-unsaturation and the reactions of the carboxylic acid functionality. Owing to these chemical aspects cinnamic acid derivatives received much attention in medicinal research as traditional as well as recent synthetic antitumor agents. We observed that in spite of their rich medicinal tradition, cinnamic acid derivatives and their anticancer potentials remained underutilized for several decades since the first published clinical use in 1905. In last two decades, there has been huge attention towards various cinnamoyl derivatives and their antitumor efficacy. This review provides a comprehensive and unprecedented literature compilation concerning the synthesis and biological evaluation of various cinnamoyl acids, esters, amides, hydrazides and related derivatives in anticancer research. We envisage that our effort in this review contributes a much needed and timely addition to the literature of medicinal research