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

Carullo, Gabriele; Ahmed, Amer; Trezza, Alfonso; Spiga, Ottavia; Brizzi, Antonella; Saponara, Simona; Fusi, Fabio; Aiello, Francesca

doi:10.1016/j.bcp.2021.114429

Cited by 19 publications

(13 citation statements)

References 52 publications

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“…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.…”

Section: Chemistrymentioning

confidence: 94%

“…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).…”

Section: Generalmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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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

Brizzi

Trezza

Spiga

et al. 2021

Molbank

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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.

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Section: Chemistrymentioning

confidence: 94%

Section: Generalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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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

Brizzi

Trezza

Spiga

et al. 2021

Molbank

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“…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.…”

Section: Introductionmentioning

confidence: 99%

7-Docosahexaenoyl-Quercetin

Carullo

Sciubba

Cocco

et al. 2021

Molbank

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Fatty acids and polyphenols represent different classes of pharmacologically active molecules. Hybrid derivatives of these compounds are interesting therapeutic tools. They could be obtained using enzymatic approaches, which allow regioselective derivatizations. In this short note, the pancreatic porcine lipase was employed to mediate the regioselective synthesis of 7-docosahexaenoyl-quercetin was described. The C-7 regioisomer formation was confirmed by 1H-NMR experiment. Generally, in this approach the alcoholic OH- was preferred when present. Nevertheless, in this case, it was demonstrated that the hindrance of the acyl group is a variable to obtain a good regioselectivity in C-7 position, employing only one-step reaction.

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Current insights and future perspectives of flavonoids: A promising antihypertensive approach

Harahap,

Syahputra,

Ahmed

et al. 2024

Phytotherapy Research

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Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L‐NG‐nitro arginine methyl ester (L‐NAME), an analog of L‐arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L‐NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L‐NAME‐induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L‐NAME‐induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin‐converting enzyme (ACE) and endothelin‐1. Moreover, they exhibit anti‐inflammatory effects, attenuating inflammation‐mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L‐NAME‐induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.

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

Cited by 19 publications

References 52 publications

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

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

7-Docosahexaenoyl-Quercetin

Current insights and future perspectives of flavonoids: A promising antihypertensive approach

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