Novel triazole-pyrazine as potential antibacterial agents: Synthesis, characterization, Antibacterial activity, drug-likeness properties and molecular docking studies.

Through Williamson ether synthesis in tetrahydrofuran at room temperature, new triazole derivatives containing 3,6-di(pyridin-2-yl)pyridazin-4-yl)methanol were created. The obtained alkyne and azide derivatives were then put through a clickable reaction using copper catalyzed azide-alkyne cycloaddition reaction (CuAAC) under more environmentally friendly conditions. Through the use of NMR and IR spectroscopy and the High Resolution Mass-Spectrometry technique (HRMS), the produced compounds were examined for their antibacterial properties against both gram-positive and gram-negative bacteria. The antibacterial tests performed with these pyrazine derivatives reveal that compound 3 showed the greatest activity among the investigated compounds against the negative gram-positive Staphylococcus aureus and Streptococcus fasciens, and positive gram-negative Escherichia coli and Pseudomonas aeruginosa. Furthermore, research on drug similarity and docking studies were carried out to define their mechanism of action for their antibacterial activities on the theory that these chemicals can be a valuable paradigm for the invention and synthesis of more potent antibacterial possibilities

Synthesis, Spectroscopic Characterization, Cytotoxic Activity and Molecular Docking Studies of novel series of quinoxaline-2,3-dione Derivatives

Ce travail explore la synthèse de nouveaux dérivés basés sur l'échafaudage quinoxaline-2,3-dione pour développer un nouveau dérivé de quinoxaline biologiquement actif. Ces dérivés ont ensuite été caractérisés à l'aide de techniques spectroscopiques, notamment la RMN du ¹H, la RMN du ¹³C et la spectrométrie de masse. De plus, les propriétés cytotoxiques de chaque composé nouvellement synthétisé ont été évaluées par rapport à trois types distincts de cellules cancéreuses humaines : les cellules cancéreuses du poumon A549, les cellules cancéreuses du col de l'utérus HeLa et les fibroblastes HFF du prépuce humain. L'enquête impliquant ces cellules a révélé un impact substantiel de la durée d'exposition et de la concentration chimique sur la viabilité cellulaire. Parmi les composés testés, le composé 3b présentait la valeur IC50 la plus favorable (29,4 µM). Cela souligne son potentiel en tant que candidat principal pour une exploration plus approfondie dans la poursuite d’interventions thérapeutiques efficaces. Pour démêler les interactions moléculaires anticipées, une approche complète d’amarrage moléculaire a été utilisée. Les composés ont été systématiquement ancrés dans les sites de liaison des protéines 6G77 (associées au cancer du poumon), 1M17 (liées aux cellules Hela) et 1Z68 (liées aux cellules fibroblastiques du prépuce humain). Il est encourageant de constater que les résultats de ces études d’amarrage moléculaire se sont révélés très prometteurs. Les informations recueillies à partir des données recèlent un potentiel pour le développement d’agents antimicrobiens plus puissants

Natural Sources, Pharmacological Properties, and Health Benefits of Daucosterol: Versatility of Actions

Daucosterol is a saponin present in various natural sources, including medicinal plant families. This secondary metabolite is produced at different contents depending on species, extraction techniques, and plant parts used. Currently, daucosterol has been tested and explored for its various biological activities. The results reveal potential pharmacological properties such as antioxidant, antidiabetic, hypolipidemic, anti-inflammatory, immunomodulatory, neuroprotective, and anticancer. Indeed, daucosterol possesses important anticancer effects in many signaling pathways, such as an increase in pro-apoptotic proteins Bax and Bcl2, a decrease in the Bcl-2/Bax ratio, upregulation of the phosphatase and tensin homolog (PTEN) gene, inhibition of the PI3K/Akt pathway, and distortion of cell-cycle progression and tumor cell evolution. Its neuroprotective effect is via decreased caspase-3 activation in neurons and during simulated reperfusion (OGD/R), increased IGF1 protein expression (decreasing the downregulation of p-AKT3 and p-GSK-3b4), and activation of the AKT5 signaling pathway. At the same time, daucosterol inhibits key glucose metabolism enzymes to keep blood sugar levels within normal ranges. Therefore, this review describes the principal research on the pharmacological activities of daucosterol and the mechanisms of action underlying some of these effects. Moreover, further investigation of pharmacodynamics, pharmacokinetics, and toxicology are suggested