A multitarget semi-synthetic derivative of the flavonoid morin with improved in vitro vasorelaxant activity: Role of CaV1.2 and KCa1.1 channels

2-Hydroxy-5-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate: Synthesis, In Silico Analysis and In Vitro Pharmacological Evaluation

“…The purification of the raw reaction material represented the limiting step to obtaining the desired product in high yield. However, the C-3 ferulic ester of quercetin was the only coupling product isolated as demonstrated by NMR experiments ( 1 H, 13 C, HSQC and HMBC), mass spectra and elemental analysis (see Supplementary Material). No other mono-O-substituted ester regioisomers were isolated and identified while traces of a diacylated product of quercetin (653 [M − H] − ) and the homocoupling product of ferulic acid (369 [M − H] − ) were detected.…”

“…Its identity was unambiguously verified by nuclear magnetic resonance and mass spectroscopy. 1 H-NMR and 13 C-NMR spectra as well as 2D-NMR experiments (HSQC and HMBC) were recorded on a Bruker Advance (Milan, Italy) operating at 600 MHz in the indicated solvent at 25 • C, and chemical shifts were expressed as δ (ppm) and the coupling constants (J) in Hz. Mass spectra were acquired in positive mode (mass range m/z of 150-1500) using a chromatography-mass spectrometry (LC-MS) apparatus (Agilent 1100, supplied with a binary high-pressure gradient pump (flow rate of 0.4 mL/min, solvent system of 95/5 methanol/water), a solvent degassing unit, and a UV detection (254 nm).…”

“…Noticeably, a close relationship between chemical modifications and activity within quercetin family is reported and exploited both to generate functional diversity and to overcome stability and bioavailability limits [10]. 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 2-phenyl-4H-chromen-4-one core. Accordingly, ferulic acid, a cinnamic-derived plant metabolite abundant in foods, is considered a protective agent with a very versatile and safe pharmacological profile [15].…”

“…1 H-and13 C-NMR (600 MHz, DMSO-d6) chemical shifts of the protons and carbons of quercetin (Que) and 3′-ferulic quercetin ester (Compd. 1).…”

7-Docosahexaenoyl-Quercetin

“…A recent study reported how fish oil, constituted by high amounts of eicosapentaenoic and docosahexaenoic (DHA) acids, could be enriched with the flavonol quercetin that reacted with these PUFAs to form the corresponding C3-esters, limiting lipid oxidation [4]. Over the years, several synthetic strategies have been proposed to synthesize lipophilic and aromatic derivatives of polyphenols, especially flavonoids [5,6]. Nevertheless, classical chemical methods led to the formation of side products, limiting the yield and purity of final compounds.…”