Abstract
Quercetin and ferulic acid are two phytochemicals extensively represented in the plant kingdom and daily consumed in considerable amounts through diets. Due to a common phenolic structure, these two molecules share several pharmacological properties, e.g., antioxidant and free radical scavenging, anti-cancer, anti-inflammatory, anti-arrhythmic, and vasorelaxant. The aim of the present work was the combination of the two molecules in a single chemical entity, conceivably endowed with more efficacious vasorelaxant activity. Preliminary in silico studies herein described suggested that the new hybrid compound bound spontaneously and with high affinity on the KCa1.1 channel. Thus, the synthesis of the 3′-ferulic ester derivative of quercetin was achieved and its structure confirmed by 1H- and 13C-NMR spectra, HSQC and HMBC experiments, mass spectrometry, and elementary analysis. The effect of the new hybrid compound on vascular KCa1.1 and CaV1.2 channels revealed a partial loss of the stimulatory activity that characterizes the parent compound quercetin. Therefore, further studies are necessary to identify a better strategy to improve the vascular properties of this flavonoid.
Highlights
Plant-derived secondary metabolites are non-nutrient compounds that aroused research interest due to their heterogeneous chemical structures complementary to a myriad of pharmacological activities
A rational docking simulation was carried out within the KCa 1.1 channel binding site proposed by Carullo and colleagues [12]
The interaction network analysis was evaluated by the protein-ligand interaction profile (PLIP) tool
Summary
Plant-derived secondary metabolites are non-nutrient compounds that aroused research interest due to their heterogeneous chemical structures complementary to a myriad of pharmacological activities In this scenario, quercetin, one of the most studied and wellknown phytochemicals, is the flavonol that exhibits many interesting healthy properties, on the cardiovascular system [1]. The modulatory effects of quercetin on CaV 1.2 and KCa 1.1 channels, playing a fundamental role in the regulation of vascular smooth muscle tone, have been comprehensively described [6,7]. In this context, drugs endowed with vascular bifunctional activity (namely, stimulation of KCa 1.1 and inhibition of CaV 1.2 channels) are of potential interest for the treatment of systemic hypertension. In the search for novel flavonoid derivatives [11,12,13,14], the acylation approach came out as an effective tool for obtaining hybrid compounds selectively decorated with a natural acid residue in the polyhydroxylated
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