Design, synthesis and pharmacological evaluation of ester-based quercetin derivatives as selective vascular KCa1.1 channel stimulators

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

doi:10.1016/j.bioorg.2020.104404

Cited by 23 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An in silico docking approach was followed to evaluate the potential activity of both mono-ferulic ester derivatives of quercetin, compound 1, i.e., 3 -O-feruloyl derivative, and compound 2, i.e., the 4 -O-feruloyl derivative, on K Ca 1.1 channels. A rational docking simulation was carried out within the K Ca 1.1 channel binding site proposed by Carullo and colleagues [12]. The docking result showed that both compounds bound spontaneously to the target, exhibiting a not significantly different binding free energy (−8.7 kcal/mol for compound 1 and −9.1 kcal/mol for compound 2) and a docking pose very similar within the binding pocket (Figure 1B).…”

Section: In Silico Analysismentioning

confidence: 89%

“…The interaction network analysis was evaluated by the protein-ligand interaction profile (PLIP) tool. Compound 1 was able to bind in a sensing region of the K Ca 1.1 channel, triggering several interactions with the target key residues [12,17] (Figure 1C and Table S1). Analogously, compound 2 triggered different interactions inside the target binding site (Figure 1D), forming an interaction network with residues identified as crucial for K Ca 1.1 channel activity [12,17] (Table S1).…”

Section: In Silico Analysismentioning

confidence: 99%

“…Compound 1 was able to bind in a sensing region of the K Ca 1.1 channel, triggering several interactions with the target key residues [12,17] (Figure 1C and Table S1). Analogously, compound 2 triggered different interactions inside the target binding site (Figure 1D), forming an interaction network with residues identified as crucial for K Ca 1.1 channel activity [12,17] (Table S1). The high binding affinity and the wide interaction network of compounds 1 and 2 in a sensing region of the K Ca 1.1 channel located in the S6/RCK linker [18], would support the hypothesis of a potential modulating activity of our derivatives against K Ca 1.1 channel.…”

Section: In Silico Analysismentioning

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%

See 3 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: In Silico Analysismentioning

confidence: 89%

Section: In Silico Analysismentioning

confidence: 99%

Section: In Silico Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, food and plant wastes represent interesting sources of biologically active molecules [18][19][20][21][22][23][24] and have been proposed as indigenous remedies [25,26]. Specifically, secondary metabolites from plants represent valuable bioactive ingredients [27][28][29][30] with remarkable antibacterial properties [31,32], useful in the treatment of several diseases. Table 1 summarizes the main natural extracts proposed for their antimicrobial features.…”

Section: Natural Extracts With Antimicrobial Activitymentioning

confidence: 99%

Nanotechnologies: An Innovative Tool to Release Natural Extracts with Antimicrobial Properties

et al. 2021

Self Cite

View full text Add to dashboard Cite

Site-Specific release of active molecules with antimicrobial activity spurred the interest in the development of innovative polymeric nanocarriers. In the preparation of polymeric devices, nanotechnologies usually overcome the inconvenience frequently related to other synthetic strategies. High performing nanocarriers were synthesized using a wide range of starting polymer structures, with tailored features and great chemical versatility. Over the last decade, many antimicrobial substances originating from plants, herbs, and agro-food waste by-products were deeply investigated, significantly catching the interest of the scientific community. In this review, the most innovative strategies to synthesize nanodevices able to release antimicrobial natural extracts were discussed. In this regard, the properties and structure of the starting polymers, either synthetic or natural, as well as the antimicrobial activity of the biomolecules were deeply investigated, outlining the right combination able to inhibit pathogens in specific biological compartments.

show abstract

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

Harahap,

Syahputra,

Ahmed

et al. 2024

Phytotherapy Research

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Design, synthesis and pharmacological evaluation of ester-based quercetin derivatives as selective vascular KCa1.1 channel stimulators

Cited by 23 publications

References 45 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

Nanotechnologies: An Innovative Tool to Release Natural Extracts with Antimicrobial Properties

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

Contact Info

Product

Resources

About