New flavonoid-based compound synthesis strategy for antihypertensive drug development

Loh, Yean Chun; Chan, Sock Ying; Tew, Wan Yin; Oo, Chuan Wei; Yam, Mun Fei

doi:10.1016/j.lfs.2020.117512

Cited by 20 publications

(15 citation statements)

References 96 publications

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“…On average, flavonoids are consumed daily from diet at approximately 400 mg/kg aglycone equivalent (AE). They have been reported to exhibit diverse therapeutic potential in medicine and other biological activities [ 12 , 13 , 14 ]. The potential of flavonoids in alleviating diabetic cardiomyopathy or other cardiovascular complications derived from diabetes have been commonly related with their remedial actions as anti-hyperglycemic [ 15 ], anti-hyperlipidemic [ 16 ], antioxidant [ 17 ], anti-inflammatory [ 18 ], and anti-apoptotic [ 19 ] agents.…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

Jubaidi

Zainalabidin

Taib

et al. 2021

IJMS

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Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

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Section: Introductionmentioning

confidence: 99%

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

Jubaidi

Zainalabidin

Taib

et al. 2021

IJMS

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“…39 When acetylenedicarboxylate was replaced with cinnamic and benzoic acids, 2-acyloxy-2-(chromon-3-yl)acetamides 9 were obtained. 40 Three-component reaction of 3-formylchromones 1, isocyanide, and either 4-hydroxycoumarin (10) or 4-hydroxy-6-methylpyran-2-one (11) in refl uxing toluene for 2 h gave furocoumarin and furopyranone isofl avone derivatives 12 (Scheme 2). 41 The authors suggest that the reaction proceeded as [4+1] cycloaddition of isocyanide to the Knoevenagel adduct 13 that generated in the reaction of 3-formylchromones 1 with compounds 10 and 11.…”

Section: Isofl Avone Hetero Analogs With Fi Ve-membered Heterocyclesmentioning

confidence: 99%

“…To date, more than 8000 natural and synthetic fl avonoids are described. 5 These compounds exhibit a wide range of biological activities along with low toxicity (see, for example, reviews [6][7][8][9][10][11] ). Reviews 12-14 are focused on the potential of diff erent natural compounds, including fl avonoids, to combat COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

et al. 2021

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The review is focused on recent developments of chemistry of synthetic analogs of natural compounds, isofl avone and homoisofl avone. The possible synthetic strategies to access heterocyclic analogs of these compounds starting from readily available 3-formylchromone and its derivatives (3-cyanochromone, 2-amino-3-formylchromone) and products of its condensation with simplest Cand N-nucleophiles are discussed. The structural features of the reaction products that depend on the nature of the reaction medium, structure of the starting compounds, and reagent ratio are considered. Particular attention is given to the application of the modern strategies of organic synthesis, namely green chemistry approaches, click reactions, domino reactions, etc. Examples of compounds of this group most promising for clinical application due to wide and pronounced pharmacological eff ects are given.

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“…В настоящее время описана структура примерно 8000 флавоноидов [1][2][3][4][5][6] и из этого многообразия агликонов и гликозидов лишь очень незначительное число индивидуальных веществ (примерно 2-3%) подробно изучены биохимически и фармакологически. Такой низкий процент изученности можно объяснить тем, что в подавляющем большинстве растений содержание индивидуальных веществ мизерный (0,1-2%) и их получение в достаточных количествах с целью последующего биохимического и фармакологического изучения связано с большими материальными затратами.…”

Section: результаты и обсуждениеunclassified

Using Quantum-Chemical Parameters for Predicting Antiradical (Ho•) Activity of Related Structures Containing a Cinnamoil Fragment. Iv. Structure-Activity Relationship Between Unsaturation Indices and Flavone Derivatives With Floroglucin Ring “A”

Оганесян

Shatokhin

2021

Farm. farmakol. (Pâtigorsk)

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The quantum-chemical parameters of 52 derivatives related to flavanones, flavanonoles, flavones and flavonoles with a phloroglucinic type of the A ring and containing electron-donating substituents in the B ring were studied.The aim is the analysis of the dynamics of changes in the electron density, bond numbers, free valence indices and unsaturation indices on carbon atoms C-7 → C-8 of the vinyl group of the main conjugation chain in relation to the position and number of substituents in the “B” ring and the type of the pharmacological activity.Materials and methods. The quantum-chemical parameters of the 4 analyzed groups of the compounds, have been calculated by the semi-empirical method PM7 (WinMopac 2016 program) on the workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM.Results and discussion. When comparing the quantum chemical parameters of the analyzed compounds, it was established that when the C-7 → C-8 multiple bond is formed, the free valency and unsaturation indices increase on both carbon atoms of the vinylene group in flavones and flavonols compared to the corresponding flavanones and flavanonols. This is explained by the fact that the value of the bond numbers Nµ on these atoms, on the contrary, decreases (Fµ = 4.732-Nµ). The transition from flavanone to flavone is accompanied by the formation of a vinyl group C-7 → C-8, and therefore both atoms from the sp3-hybridized state go into the sp2-state. The consequence of this transformation is a change in the electronegativity value and an increase in the unsaturation index of C-7 and C-8 atoms: C sp3 = 2.5; Csp2 = 2.8. At the same time, the transition from flavanone to flavone leads to the formation of a conjugated system with the participation of π-electrons of the aromatic system “B”, C-7, C-8 atoms and the carbonyl group, which is commonly called the “main conjugation chain”. These structural changes, namely, the transition from a less oxidized flavanone to a more oxidized flavone, contribute to a decrease in the electron density on C-7 and C-8 atoms, and an increase in the total unsaturation of the molecules in general. Mulliken charges on C-7 of all groups of compounds are characterized by a positive value. As for the carbon atoms of the B fragment, the following features are revealed here: in the presence of one substituent -OH or -OCH3 on the carbon atom to which the substituent is bounded, the Mulliken charge is positive; if there are two substituents in the B ring -OH or -OCH3, as well as two -OCH3 groups, then the carbon atoms bonded to the indicated substituents also have a positive Mulliken charge; in the case of trihydroxy substituted in the C-2, C-3 and C-4 B ring, all three carbon atoms are characterized by a positive Mulliken charge; if there are methoxy groups in positions C-2, C-3 and C-4, then the positive Mulliken charge is concentrated only on C-2 and C-4 atoms, and on C-3 atom this charge has a negative value.Conclusion. The above data on the quantum-chemical parameters of the main conjugation chain indicate that the transition of C-7 and C-8 atoms to the sp2-hybrid state, leads to a decrease in the electron density and a decrease in the bond numbers, with a simultaneous increase in the indices of unsaturation and free valence on these atoms. Thus, the trigger mechanism of the anti-radical activity, primarily with respect to the HO • radical, is determined by the fact that this particle, electrophilic in its properties, will attach in the C-8 atom during an initial attack.

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New flavonoid-based compound synthesis strategy for antihypertensive drug development

Cited by 20 publications

References 96 publications

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

Using Quantum-Chemical Parameters for Predicting Antiradical (Ho•) Activity of Related Structures Containing a Cinnamoil Fragment. Iv. Structure-Activity Relationship Between Unsaturation Indices and Flavone Derivatives With Floroglucin Ring “A”

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