Development of Robust 17(),18()-Epoxyeicosatetraenoic Acid (17,18-EEQ) Analogues as Potential Clinical Antiarrhythmic Agents.

17(),18()-Epoxyeicosatetraenoic acid (EEQ) is a cytochrome P450 metabolite of eicosapentaenoic acid (EPA) and a powerful negative chronotrope with low nanomolar activity in a neonatal rat cardiomyocyte (NRCM) arrhythmia model. Prior studies identified oxamide as a soluble epoxide hydrolase (sEH) stable replacement but unsuitable for applications due to limited oral bioavailability and metabolic stability. These ADME limitations have been addressed in an improved generation of negative chronotropes, e.

One-Pot Synthesis of Triazolo-Heterolignans: Biological Evaluation and Molecular Docking Studies as Tubulin Inhibitors.

Background: The anti-mitotic activity of podophyllotoxin derivative targeting tubulin enzyme proved them as strong polymerization inhibitors. The introduction of heteroatom along with different heteroaryl systems in naturally obtained lignans created a latitude for design of bioactive components. A novel one-pot sequential propargylation/cycloaddition reaction strategy has been followed to synthesize triazolo-heterolignans.