Acidic properties of flavonoid compounds and the choice of solvent for performing potentiometric analysis

Georgievskii, V. P.

doi:10.1007/bf00638771

Cited by 10 publications

(5 citation statements)

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“…Experimental data for quercetin allow us to state that this pentahydroxyflavone is not as acidic as reported previously by Escandar et al Its acidity is similar to that determined by Georgievskii, and the kinetic data (discussed below) confirmed that observation. A correct determination of the site of primary deprotonation of quercetin is of great importance if reaction of quercetin anion with a radical is considered.…”

Section: Resultssupporting

confidence: 85%

Acidity of Hydroxyl Groups: An Overlooked Influence on Antiradical Properties of Flavonoids

et al. 2009

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The reactions of 10 flavonoids with 2,2-diphenyl-1-picrylhydrazyl radical (dpph(*)) carried out in alcohols always occur significantly faster than in acidified alcohols or in dioxane. These fast kinetics benefit from the contribution of the electron transfer from a flavonoid anion to a radical, a mechanism known as Sequential Proton-Loss Electron-Transfer (SPLET), which adds to the kinetics of single-step Hydrogen Atom Transfer (HAT)/Proton Coupled Electron Transfer (PCET) processes (see Acc. Chem. Res. 2007, 40 , 222.). The domination of SPLET over HAT/PCET in case of a flavonoid reacting with electron-deficient radicals such as peroxyls or dpph(*) in polar solvents explains the enhancement of antioxidant activity of 3-hydroxyflavone. It also elucidates the great acceleration in the reactions of dpph(*) with quercetin, morin, galangin, and 7,8-dihydroxyflavone. The analysis of structure-acidity and structure-activity relationships for 10 flavonoids clearly indicates that hydroxyl group at position 7 is the most acidic site. Thus, in polar solvents this group can participate in radical reaction via SPLET. In nonpolar solvents the most active site in quercetin (a flavonoid antioxidant commonly found in plants) is 3',4'-dihydroxyl moiety and HAT/PCET occurs. However, in ionization-supporting solvents an anion formed at position 7 is responsible for very fast kinetics of quercetin/dpph(*) reaction because both mechanisms participate: HAT (from catechol moiety in ring B) and SPLET (from ionized 7-hydroxyl in ring A). Because of conjugation of rings A, B, and C the final structure of the formed quercetin radical (or quercetin anion radical) is the same for the SPLET and HAT/PCET mechanisms.

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Section: Resultssupporting

confidence: 85%

Acidity of Hydroxyl Groups: An Overlooked Influence on Antiradical Properties of Flavonoids

et al. 2009

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“…Chemically, almost all reported PL flavone inhibitors are related to 5-hydroxy-2-phenylchromen-4-one or 5-hydroxy-3-phenylchromen-4-one (Chart 2), which is structurally related to 2-hydroxy benzoyl /benzoic acid side chain (Buchholz & Melzig, 2015;Rahim, Takahashi, & Yamaki, 2015). The 5-hydroxy group in both structures is a highly acidic chelator group (Georgievskii, 1980). Although Our research findings, in hand with Buchholz and Melzig (2015) and Menteşe et al (2017), reveal that a carboxyl group or the hydroxyl acidic groups take part in the activity between phenolic acids and the active center of the lipase.…”

Section: Pl Inhibitory Activity: Rationalementioning

confidence: 99%

“…Chemically, almost all reported PL flavone inhibitors are related to 5‐hydroxy‐2‐phenylchromen‐4‐one or 5‐hydroxy‐3‐phenylchromen‐4‐one (Chart ), which is structurally related to 2‐hydroxy benzoyl /benzoic acid side chain (Buchholz & Melzig, ; Rahim, Takahashi, & Yamaki, ). The 5‐hydroxy group in both structures is a highly acidic chelator group (Georgievskii, ). Although many pharmaceutical activities are linked to great numbers of hydroxyl groups on the non‐sugar part, none of the pharmacologically active natural flavonoids, such as luteolin, quercetin, kaempferol, hesperetin, myricetin, and rutin, have any substitution on the acidic hydroxyl group at carbon5.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds

Mamdooh

Kasabri

Al‐Hiari

et al. 2018

Drug Development Research

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In this study, 15 commercial acidic drugs have been evaluated for pancreatic lipase (PL) inhibitory activity using an in vitro spectrophotometric method. The acidity was the basis of selection, since most PL inhibitors exhibit acidic groups and high lipophilicity. Orlistat was the robust reference agent for potency and efficacy determinations. In comparison to the cisplatin, the evaluation of the antineoplastic activities of selected drugs in a panel of colorectal cancer cell lines (HT‐29, HCT‐116, SW620, CACO‐2, and SW480) and normal periodontal ligament fibroblasts for safety examination was performed by using a sulforhodamine procuring ascorbic acid as a reference in diphenyl‐2‐picryl‐hydrazyl assay of radical scavenging properties was performed. This research revealed three highly acidic pharmacological classes with reasonable PL inhibitory activity in comparison to orlistat out of 15 selected drugs, namely sulfonylureas, fluoroquinolones, and proton pump inhibitors. Docking studies supported the hypothesis of a selection based on acidity, since it showed that the sulfonamide acid group (glyburide) is a remarkably potent interacting group with the enzyme. Failing to fulfill other structure‐activity relationship requirements (lipophilicity) led to weak activity. Since the drugs are of different chemical classes with unknown mechanisms, they showed diverse antiproliferative activity. Some drugs such as atorvastatin and gemifloxacin showed higher antiproliferative activity than cisplatin with high‐safety profiles against SW620 and SW480 cell lines, respectively, whereas lansoprazole and clopidogrel revealed comparable activity to cisplatin against HCT‐116 and SW480, respectively. Unfortunately, selected tested drugs exhibited negligible radical scavenging activity versus ascorbic acid. Hit, Lead & Candidate Discovery

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“…Q has five phenolic OHs, which have five different pKa values [ 18 ]. The pKa of Q has been studied using various methods, but no consistent value was found; namely, it varies from 6.74 [ 19 ] when determined by spectrophotometry, to 7.19 [ 20 ] when determined by capillary zone electrophoresis, and 7.71 [ 21 ]/8.21 [ 22 ] when determined by potentiometry. There is also no consensus on the pKa of the second acid group of Q, the reported value of this pKa varies from 8.4 to 9.4 [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Flow of the Redox Energy in Quercetin during Its Antioxidant Activity in Water

Moalin

Zhang

et al. 2020

IJMS

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Most studies on the antioxidant activity of flavonoids like Quercetin (Q) do not consider that it comprises a series of sequential reactions. Therefore, the present study examines how the redox energy flows through the molecule during Q’s antioxidant activity, by combining experimental data with quantum calculations. It appears that several main pathways are possible. Pivotal are subsequently: deprotonation of the 7-OH group; intramolecular hydrogen transfer from the 3-OH group to the 4-Oxygen atom; electron transfer leading to two conformers of the Q radical; deprotonation of the OH groups in the B-ring, leading to three different deprotonated Q radicals; and finally electron transfer of each deprotonated Q radical to form the corresponding quercetin quinones. The quinone in which the carbonyl groups are the most separated has the lowest energy content, and is the most abundant quinone. The pathways are also intertwined. The calculations show that Q can pick up redox energy at various sites of the molecule which explains Q’s ability to scavenge all sorts of reactive oxidizing species. In the described pathways, Q picked up, e.g., two hydroxyl radicals, which can be processed and softened by forming quercetin quinone.

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Acidic properties of flavonoid compounds and the choice of solvent for performing potentiometric analysis

Cited by 10 publications

References 1 publication

Acidity of Hydroxyl Groups: An Overlooked Influence on Antiradical Properties of Flavonoids

Acidity of Hydroxyl Groups: An Overlooked Influence on Antiradical Properties of Flavonoids

Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds

The Flow of the Redox Energy in Quercetin during Its Antioxidant Activity in Water

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