Effects of plant extracts and derivatives on cardiac K+, Nav, and Cav channels: a review.

Natural products (NPs) are endless sources of compounds for fighting against several pathologies. Many dysfunctions, including cardiovascular disorders, such as cardiac arrhythmias have their modes of action regulation of the concentration of electrolytes inside and outside the cell targeting ion channels. Here, we highlight plant extracts and secondary metabolites' effects on the treatment of related cardiac pathologies on hERG, Nav, and Cav of cardiomyocytes. The natural product's pharmacology of expressed receptors like alpha-adrenergic receptors causes an influx of Ca2+ ions through receptor-operated Ca2+ ion channels. We also examine the NPs associated with cardiac contractions such as myocardial contractility by reducing the L-type calcium current and decreasing the intracellular calcium transient, inhibiting the K+ induced contractions, decreasing amplitude of myocyte shortening and showed negative ionotropic and chronotropic effects due to decreasing cytosolic Ca2+. We examine whether the NPs block potassium channels, particular the hERG channel and regulatory effects on Nav1.7.

Advances Toward Amphidinolides C, F and U: Isolations, Synthetic Studies and Total Syntheses.

Amphidinolides C, F, and U, including C2-C4 analogs, are highly cytotoxic marine macrolides, mainly isolated from dinoflagellates of the genus Amphidinium. All these polyketides share a 75 % or more similar structure, highlighted by a macrolactone ring, at least one trans-2,5-substituted-THF motif and a characteristic polyenic side chain. From their isolation and absolute configurational assignment, the total synthesis of these marine macrolides represented an intense challenge to the organic synthesis community over the last 15 years, with around 14 research groups engaged in this inspiring task. In the first part of this review, we present the different approaches to the isolation and characterization of these natural products, including the most recent analogs, which may cast doubt on the biogenetic origin of these compounds. The various synthetic approaches to the total synthesis of C, F, and U amphidinolides are presented in a second part, focusing on key reactions and/or innovative strategies. The review concludes in a third section summarizing the successful approaches leading to the total synthesis of one of the members of this amphidinolide subfamily.

Chemical Constituents and Antimicrobial and Antioxidant Activities of Essential Oil from Dried Seeds of Xylopia aethiopica.

The study aimed to investigate the chemical composition and antimicrobial and antioxidant activities of the essential oil from dried seeds of Xylopia aethiopica. The essential oil was obtained by hydrodistillation and analyzed by GC/FID and GC/MS. The essential oil yield was 1.35%. Forty-nine compounds were identified in the essential oil with 1,8-cineole (16.3%), ß-pinene (14.8%), trans-pinocarveol (9.1%), myrtenol (8.3%), α-pinene (5.9%), and terpinen-4-ol (5.6%) as major components. The antimicrobial activity of this essential oil was studied using disk diffusion and broth microdilution methods on four bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa) and one fungus (Candida albicans). The essential oil exhibited excellent activity against S. aureus, E. faecalis, and C. albicans and moderate activity against E. coli. Among all strains tested, C. albicans showed the best sensitivity with a MIC of 50 mg/mL. The antioxidant activity was examined using a DPPH-free radical scavenging assay. The essential oil of X. aethiopica showed low antioxidant activity (IC50 = 784.604 ± 0.320 mg/mL) compared to that of ascorbic acid and the reference compound (IC50 = 0.163 ± 0.003 mg/mL). The results indicate that consumption of X. aethiopica seeds can reduce the virulence of food-borne pathogens and their resistance to antibiotics.

Amphidinolides F and C2: An Odyssey in Total Synthesis.

Amphidinolides F, C, C2, and C3 are marine natural products isolated from dinoflagellates Amphidinium species. They share the same macrolactone core, with the difference between them residing at the side chain level. A predominant feature of these amphidinolides is the presence of two trans-THF rings inside the macrolactone core, which is thought to be built by C-glycosylation with titanium enolate of N-acetyl oxazolinethiones. Thus, the original strategy for their total synthesis was based on the assembly of three main fragments corresponding to C1-C9, C10-C19, and C20-C29 or C20-C34 disconnections. Whereas synthesis of all fragments was successful, the C-glycosylation reaction between C19 and C20 turned out to be an issue. Therefore, a second route was designed. The new disconnection between C17 and C18 was based on a sulfone addition and a desulfonylation sequence. Our convergent strategy allowed the total synthesis of amphidinolide F and enabled a new unifying route toward the synthesis of amphidinolides C, C2, and C3 using a late-stage divergent approach. Although there were unsatisfying yields at some critical steps, our work culminated into the first total synthesis of amphidinolide C2.

Access to a Library of 1,3-disubstituted-1,2,3-triazenes and Evaluation of their Antimicrobial Properties.

BACKGROUND: Due to the rapid development of microbial resistance, finding new molecules became urgent to counteract this problem. OBJECTIVE: The objective of this work is to access 1,2,3-triazene-1,3-disubstituted, a class of molecule with high therapeutic potential. METHODS: Here we describe the access to 17 new triazene including six with an imidazole-1,2,3-triazene moiety and eleven with an alkyl-1,2,3-triazene moiety and their evaluation against five strains: two gram (-): Escherichia coli ATCC 25921 and Pseudomonas aeruginosa ATCC 27253; two gram (+) : Staphylococcus aureus ATCC 38213 and Enterococcus faecalis ATCC 29212; and one fungi: Candida albicans ATCC 24433. RESULTS: All strains were sensitive and the best MIC, 0.28 µM, is observed for 4c against Escherichia coli ATCC 25921. Compound 9, 3-isopropynyltriazene, appears to be the most interesting since it is active on the five evaluated strains with satisfactory MIC 0.32 µM against Escherichia coli and Pseudomonas aeruginosa and 0.64 µM against Enterococcus faecalis and Pseudomonas aeruginosa. CONCLUSION: Comparing the structure activity relationship, electron withdrawing groups appear to increase antimicrobial activity.