Analogues of xanthones——Chalcones and bis-chalcones as α-glucosidase inhibitors and anti-diabetes candidates

Cai, Chao-Yun; Rao, Li; Rao, Yong; Guo, Jin-Xuan; Xiao, Zhi-Zun; Cao, Jingyu; Huang, Zhi‐Shu; Wang, Bo

doi:10.1016/j.ejmech.2017.02.007

Cited by 84 publications

(43 citation statements)

References 20 publications

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“…The compounds were divided as chalcones 1-28, with the 1,3-diarylprop-2-en-1-one framework, and chalcone analogues 29-41, known as cinnamylideneacetophenones, which hold two double bonds linking the A and B rings. In the first set of compounds (1-28), one is unsubstituted (1), four are hydroxylated (2-5), ten are hydroxylated and methoxylated (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), two are only methoxylated (16,17), two display methyl substituents (18,19), two display nitro groups (20,21) and seven possess chloro substituents (22)(23)(24)(25)(26)(27)(28). Among the chalcone analogues (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), one is unsubstituted (29), eleven present a single substitution, including methyl (30,36), methoxy (31,37), chloro (32), fluoro (33), bromo (34), nitro (35,38,39) and hydroxy…”

Section: In Vitro α-Amylase Inhibitionmentioning

confidence: 99%

“…15,18,19 Several reports even indicate that some chalcones are able to inhibit the enzymes α-amylase [20][21][22][23][24] and α-glucosidase. 20,22,[25][26][27][28][29] However, differences found in the experimental conditions regarding this topic, together with the fact that the authors usually constrained the study to a limited number of compounds with decreased rational drug design, make the comparison among the available studies difficult and consequently the establishment of an accurate structure-activity relationship (SAR). With this aim, the inhibitory activity of a panel of twenty-eight chalcones and thirteen chalcone analogues against α-amylase and α-glucosidase, a total of forty-one structurally related scaffolds (Table 1), most of them being studied here for the first time, is assessed.…”

Section: Introductionmentioning

confidence: 99%

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A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

et al. 2019

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Section: In Vitro α-Amylase Inhibitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

et al. 2019

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“…). An AB two‐spin system overlapping with a typical trans coupling of 3 J AB = 12–18 Hz confirms a CC double bond with protons in trans configuration . 1 H NMR spectra of chalcone 1a showed one doublet at 7.58–7.61 ppm ( 3 J AB = 5.7) for the CHC and another doublet at 6.75–6.78 ppm ( 3 J AB = 15.7 Hz) for the COCH, indicating that the ethylene moiety in the enone linkage is in the trans conformation.…”

Section: Resultsmentioning

confidence: 78%

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

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A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED ), 285.02 and 293.42 mg/kg (scPTZ ED ), and 389.11 and 412.16 mg/kg (TD ), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

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“…However, 2´,4´‐dihydroxychalcone and 2´,4´‐dihydroxy‐3´‐methoxychalcone isolated from PEs were most active, inhibiting lipase and α‐glucosidase enzymes (Table 3). Other authors reported that chalcones are potent α‐glucosidase, α‐amylase, and lipase inhibitors (Bale et al., 2018; Cai et al., 2017; Mahapatra, Asati, & Bharti, 2015, Mahapatra, & Barthi, 2016).…”

Section: Resultsmentioning

confidence: 99%

“…Cai et al. (2017) reported that the hydroxyl chalcones showed a higher activity on α‐glucosidase than methoxylated chalcones and that the position of hydroxyl groups in chalcones is another key factor for their α‐glucosidase inhibitory activities, probably due to its H‐bond donor effect. The inhibition of amylase might be due to the availability of the electron‐accepting groups and electron‐donating groups (Bale et al., 2018).…”

Section: Resultsmentioning

confidence: 99%

Zuccagnia‐type Propolis from Argentina: A potential functional ingredient in food to pathologies associated to metabolic syndrome and oxidative stress

Salas

Mercado

Orqueda

et al. 2020

Journal of Food Science

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The effect of Argentine propolis extracts against enzymes related to metabolic syndrome and oxidative stress, as well as the botanical origin of raw propolis, were studied. Histological and chemical analyses of propolis samples revealed that the botanical origin is Zuccagnia punctata, an Argentine medicinal plant. The melissopalynological analysis showed both pollen grains of Z. punctata and the other plant species. This result indicates that the differences found in the botanical remains compared to the palynological studies may have been caused by the bees selecting resinous shrubs mainly of Z. punctata for the production of propolis and other plants with flowers for the production of honey. The richness of propolis was remarkable in two flavonoid precursors (2´,4´‐dihydroxy‐3´‐methoxychalcone, 2´,4´‐dihydroxychalcone), the major chemical components of Z. punctata. The hydroalcoholic extracts of Argentine propolis and Z. punctata were able to inhibit enzymes associated with the metabolic syndrome, including α‐glucosidase, α‐amylase and lipase, with IC50 values between 7 to 14, 37 to 48, and 13 to 28 µg/mL, respectively. Biological activity was mainly attributed to chalcones. Oxygen and nitrogen reactive species scavenging activity was determined by the assays of superoxide radical (O2•−), hydroxyl radical (HO•), hydrogen peroxide (H2O2), nitric oxide (NO•), and cation radical (ABTS•+). Results showed SC50 values between 115 to 278, 12.50 to 46; 39 to 92; 50 to 104.50 and 23 to 33.75 µg/mL, respectively. This study suggests for the first time that propolis from Argentina is highly effective in inhibiting enzymes related to the metabolic syndrome and in free‐radical scavenging that would justify its use as a dietary supplement or as a functional ingredient in special food. Practical Application Propolis from Catamarca, Argentina, is traditionally used as medicine and food. Its botanical origin is Zuccagnia punctata, an endemic plant species popularly used as a medicine in Argentina. Propolis has the ability to regulate the activity of enzymes involved in the carbohydrate and lipid metabolism, and consequently in metabolic syndrome. Besides, its antioxidant capacity makes it a natural product that can be used as a dietary supplement or as a functional ingredient in special foods. It is important to highlight that in the Argentine Food Code, propolis was incorporated in 2008 as a dietary supplement and the present results give major added value to this product.

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Analogues of xanthones——Chalcones and bis-chalcones as α-glucosidase inhibitors and anti-diabetes candidates

Cited by 84 publications

References 20 publications

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Zuccagnia‐type Propolis from Argentina: A potential functional ingredient in food to pathologies associated to metabolic syndrome and oxidative stress

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