Design, Synthesis and Preliminary Evaluation of Novel Imperatorin Derivatives as Vasorelaxant Agents

Na      Li; Jianyu      He; Yingzhuan      Zhan; Nan      Zhou; Jie      Zhang

Abstract

A series of novel imperatorin derivatives were synthesized from commercially available xanthotoxin. The in vitro pharmacological evaluation indicated that all of the compounds possessed potent vasodilatory activity. Among them, compounds (5b), (5d) and (5e) exhibited higher vasdilatory activity (with EC50 values of 0.68 μM, 0.59 μM and 0.49 μM, respectively) than imperatorin (EC50 = 1.12 μM). The program Volsurf was used to predict the derivatives' ADME relevant descriptors. The results suggested that these novel compounds had a potential interest for the development of novel and potent vasorelaxant agents.

Keywords: Imperatorin derivatives, vasodilatory activity, hypertension, vasorelaxant agents, xanthotoxin, cardiovascular disease, atherogenesis, cardiovascular morbidity, anti-inflammatory, anticancer, antivirus, anti-HIV, anti-fungal, antibacterial, antioxidant, secretase inhibitory, hepatoprotective activities, vascular smooth mus-cle/cell, membrane chromatography, gas chromatography/mass, spectrometry, antiaggregatory activity, boron tribro-mide, nicardipine, mesenteric artery, endothelium, olefinc bond, bioavailability, adsorption, distribution, metabo-lism, excretion (ADME), drug design, pharmacokinetic properties, Lipinski's rule, blood-brain barrier, Caco-2 permeation experiment, Volsurf, structure-activity relationship, thin layer chroma-tography, 1H-NMR spectra, Xanthoxol, etherification, Anhydrous potassium carbonate, column chromatography, vasoconstrictor, nonlinear regression, GraphPad Prism