Α-amylase Inhibition Research Articles

Discovery of new anti-diabetic potential agents based on paracetamol incorporating sulfa-drugs: Design, synthesis, α-amylase, and α-glucosidase inhibitors with molecular docking simulation

Uncontrolled diabetes can lead to hyperglycemia, which causes neuropathy, heart attacks, retinopathy, and nervous system damage over time, therefore, controlling hyperglycemia using potential drug target inhibitors is a promising strategy. This work focused on synthesizing new derivatives via the diazo group, using a hybridization strategy involving two approved drugs, paracetamol and several sulfonamides. The newly designed diazo-paracetamols 5–12 were fully characterized and then screened for in vitro α-amylase and α-glucosidase activities and exhibited inhibitory percentages (IP) = 92.5–96.5 % and 91.0–95.7 % compared to Acarbose IP = 96.5 and 95.8 %, respectively at 100 μg/mL. The IC50 values of the synthesized derivatives were evaluated against α-amylase and α-glucosidase enzymes, and the results demonstrated moderate to potent activity. Among the tested diazo-paracetamols, compound 11 was found to have the highest potency activity against α-amylase with IC50 value of 0.98 ± 0.015 μM compared to Acarbose IC50 = 0.43 ± 0.009 μM, followed by compound 10 (IC50 = 1.55 ± 0.022 μM) and compound 9 (IC50 = 1.59 ± 0.023 μM). On the other hand, for α-glucosidase, compound 10 with pyrimidine moiety demonstrated the highest inhibitory activity with IC50 = 1.39 ± 0.021 μM relative to Acarbose IC50 = 1.24 ± 0.029 μM and the order of the most active derivatives was 10 >9 (IC50 = 2.95 ± 0.046 μM) >11 (IC50 = 5.13 ± 0.082 μM). SAR analysis confirmed that the presence of 4,5-dimethyl-isoxazole or pyrimidine nucleus attached to the sulfonyl group is important for activity. Finally, the docking simulation was achieved to determine the mode of binding interactions for the most active derivatives in the enzyme's active site.

Ultrasonic-Assisted Extraction and Gastrointestinal Digestion Characteristics of Polysaccharides Extracted from Mallotus oblongfolius

The polysaccharides were extracted from the leaves of Mallotus oblongifolius (MO) using an ultrasonic-assisted extraction method in this study. The main variables affecting the yield of polysaccharides extracted from Mallotus appallatus (MOPS) were identified and optimized while concurrently investigating its antioxidant capacity, hypoglycemic activity, and digestive properties. The results indicated that the optimal ultrasound-assisted extraction of MOPS involved an ultrasound power of 200 W, a liquid-to-solid ratio of 25:1 (mL:g), an extraction temperature of 75 °C, and an ultrasound time of 45 min, leading to an extraction yield of (7.36 ± 0.45)% (m/m). The MOPS extract exhibited significant scavenging activity against DPPH and ABTS radicals with IC50 values of (25.65 ± 0.53) μg/mL and (100.38 ± 0.38) μg/mL, respectively. Furthermore, it effectively inhibited the enzymatic activities of α-glucosidase and α-amylase with IC50 values of (2.27 ± 0.07) mg/mL and (0.57 ± 0.04) mg/mL, respectively. The content of MOPS remained relatively stable in the stomach and small intestine; however, their ability to scavenge DPPH radicals and ABTS radicals and exhibit reducing power was attenuated, and the inhibition of α-amylase and α-glucosidase activity was diminished. In conclusion, the ultrasonic extraction of MOPS showed feasibility and revealed antioxidant and hypoglycemic effects. However, the activities were significantly reduced after gastric and small intestinal digestion despite no significant change in the MOPS content.

Synthesis, biological evaluation and in silico molecular modelling studies of chloro substituted bis-indole containing benzohydrazide analogues as potential anti-diabetic and anti-Alzheimer's agents

Fifteen bis-indolylmethane analogues were synthesized, characterized through NMR (1H, 13C) and high-resolution electron-impact mass spectrometry (HREI-MS), and tested against α-glucosidase, α-amylase, acetylcholinesterase, and butyrylcholinesterase inhibitory potentials. All analogues exhibited different inhibitory potentials, with IC50 values ranging between 7.5 ± 0.92 to 58.4 ± 0.07 μM (α-glucosidase), and 0.80 ± 0.05 to 15.30 ± 0.10 μM (α-amylase) as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 and 8.90 ± 0.10 μM). Out of fifteen analogues, nine showed an excellent inhibitory potency that was manyfold better than standard drugs. A slight increase or decrease in inhibition was observed due to substituents attached at imine site. In the case of α-amylase inhibition, two analogues such as 2 and 11, showed excellent inhibitory potential with IC50 values of 0.80 ± 0.05 and 0.90 ± 0.10 μM while all other analogues showed good potency. All analogues were also tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potentials, and they showed good potentials ranging from 1.40 ± 0.20 to 16.20 ± 0.50 μM (AChE) and 3.20 ± 0.10 to 19.60 ± 0.20 μM (BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 μM and 4.5 ± 0.11 μM). In the case of AChE, analogue 3 is the most potent, and in the case of BuChE, analogue 9 is the most potent among the series. The structure-activity relationship was carried out, mainly associated with the nature, number, and position and the electron-donating and electron-withdrawing effects of the substituent(s) on the phenyl ring. The binding modes as well as binding free energy for α-glucosidase and α-amylase inhibitors were determined through docking studies.

Combination of plant metabolites hinders starch digestion and glucose absorption while facilitating insulin sensitivity to diabetes.

Diabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications. To overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity. The results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM. The results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity.

Synthesis, Biological Activity Studies and Molecular Modeling Studies of Chalcone Compounds with Methyl Group

A series of new chalcone derivatives (1-5) were synthesized as a result of the Claisen-Schmidt condensation of different substituted methyl aldehydes of 4′-Piperazinoacetophenone. Anticholinesterase (AChE and BChE) inhibitory activity and antidiabetic (α-glucosidase and α-amylase inhibitory) activities of the synthesized compounds were examined. While compound 1 is the most active molecule in AChE (IC50= 16.29±0.44 μM), BChE (IC50 = 10.19±0.04 μM) and α-amylase (IC50= 105.51±0.24 μM) inhibitor activities; Compound 5 was found to be the most active molecule in α-glucosidase inhibitor activity. In silico and molecular docking studies of compounds 1-5 were performed. According to molecular docking results, all molecules were found to be more active than the reference compounds.

Evaluation of the Anti-diabetic Activity of Purified Compounds of Ferula assafoetida by in vitro and in silico Methods

Objective Postprandial hyperglycemia is considered an early sign of diabetes. Enzyme inhibitors, such as α-amylase and α-glucosidase inhibitors, are currently being studied as potential drugs for preventing postprandial hyperglycemia. Methods In this study, we investigated the effects of four purified 7-hydroxycoumarine derivatives from Ferula assafoetida: umbelliprenin, farnesiferol A, farnesiferol C, and samarcandin. We evaluated cell toxicity using the MTT method and also examined glucose uptake and inhibition of α-amylase and α-glucosidase enzymes in vitro. Additionally, we conducted a molecular docking study to investigate the mechanism of enzyme inhibition. Results The cell toxicity of the terpenoid coumarin derivatives (umbelliprenin, farnesiferol A, farnesiferol C, and samarcandin) on HepG2 cells was found to be approximately 28 to 37 µg/ml. The glucose uptake assay showed that these compounds (at a concentration of 25 µg/ml) were able to increase glucose consumption by HepG2 cells to a level comparable to that of the positive control (metformin at 50 µg/ml). Furthermore, umbelliprenin significantly inhibited the activity of α-amylase and α-glucosidase (by 35.07% and 4.98%, respectively). Molecular docking results indicated that umbelliprenin, with a farnesyl chain, had a more potent inhibitory effect. Conclusion Our findings suggest that umbelliprenin may be a valuable compound for controlling postprandial hyperglycemia and diabetes. However, further in vivo studies and clinical trials are necessary to validate these effects. While this research offers potential for the development of more effective compounds with coumarin structures, further studies are needed to confirm these findings.

Phytochemical analysis, antioxidant, acetylcholinesterase, and α-amylase inhibitors from extract.

To investigate the effects of Hippeastrum hybridum (HH) as a free radical scavenger, and an inhibitor of the two enzymes i-e Alpha-amylase (α-amylase) and acetylcholinesterase (AChE). In this study, HH plant was preliminary analyzed for phytochemical screening and then tested for its antioxidant, anti-α-amylase, and anti-AChE efficiency via standard procedures. Phytochemical analysis shows the existence of different compounds; while Coumarins and quinones were absent. The total phenolic, flavonoid, and tannins content were found to be (78.52 ± 0.69) mg GAE/g, (2.01 ± 0.04) mg RUE/g, and (58.12 ± 0.23) mg TAE/g of plant extract respectively. 28.02% ± 0.02% alkaloid and 2.02% ± 0.05% saponins were present in the HH extract. The HH extract showed the anti-oxidant property with IC50 (50% inhibition) of (151.01 ± 0.13) (HH), (79.01 ± 0.04) (Ascorbic acid) for ferric reducing, (91.48 ± 0.13) (HH), (48.02 ± 0.11) (Ascorbic acid) against Ammonium molybdenum, (156.02 ± 0.31) (HH), (52.38 ± 0.21) (Ascorbic acid) against DPPH, 136.01 ± 0.21 (HH), 52.02± 0.31 (Ascorbic acid) against H2O2, and 154.12 ± 0.03 (HH), (40.05 ± 0.15) (Ascorbic acid) μg/mL against ABTS respectively. Statistical analysis indicated that HH caused a competitive type of inhibition of α-amylase (Vmax remained constant and Km increases from 10.65 to 84.37%) while Glucophage caused the un-competitive type of inhibition i-e both Km and Vmax decreased from 40.49 to 69.15% and 38.86 to 69.61% respectively. The Ki, (inhibition constant); KI, (dissociation constant), Km, (Michaelis-Menten constant), and IC50 were found to be 62, 364, 68.1, and 38.08 ± 0.22 for HH and 12, 101.05, 195, 34.01 ± 0.21 for Glucophage. Similarly, HH causes an anon-competitive type of inhibition of AChE i-e Km remains constant while Vmax decreases from 60.5% to 74.1%. The calculated Ki, KI, Km, and IC50 were found to be 32, 36.2, 0.05, and 18.117 ± 0.018. From the current results, it is concluded that HH extract contains bioactive compounds, and could be a good alternative to controlling oxidants, Alzheimer's and Type-II diabetic diseases.

Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α-glucosidase, α-amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation.

A new series of quinoxaline-sulfonamide derivatives 3-12 were synthesized using fragment-based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline-sulfonamide derivatives were evaluated for antidiabetic and anti-Alzheimer's potential against α-glucosidase, α-amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against α-amylase and α-glucosidase with inhibitory percentages between 24.34 ± 0.01%-63.09 ± 0.02% and 28.95 ± 0.04%-75.36 ± 0.01%, respectively. Surprisingly, bis-sulfonamide quinoxaline derivative 4 revealed the most potent activity with inhibitory percentages of 75.36 ± 0.01% and 63.09 ± 0.02% against α-glucosidase and α-amylase compared to acarbose (IP = 57.79 ± 0.01% and 67.33 ± 0.01%), respectively. Moreover, the quinoxaline derivative 3 exhibited potency as α-glucosidase and α-amylase inhibitory with a minute decline from compound 4 and acarbose with inhibitory percentages of 44.93 ± 0.01% and 38.95 ± 0.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide-quinoxaline derivative 3 emerged as the most active member with inhibitory percentage of 41.92 ± 0.02% compared with donepezil (IP = 67.27 ± 0.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.

Alpha-amylase Inhibitory and Cytotoxicity Investigation of Biologically Synthesized Silver Nanoparticles Using Balanites aegyptiaca on C2C12 Cells

Introduction: Silver nanoparticles were biologically synthesized from the leaf and seed extract of Balanites aegyptiaca against diabetes. Method: The silver nanoparticles were characterized using UV-visible spectroscopy, FTIR, SEM, TEM, zeta potential and dynamic light scattering for size distribution. The finding proved the nanosize and spherical shapes of the nanoparticles. In-vitro antidiabetic and cytotoxic activities of the synthesized nanoparticles were evaluated for the first time in both the plant extract, and they showed significant inhibition of α-amylase. However, the inhibition was elevated in the case of nanoparticles. Result: It was found that seed and leaf extract inhibited α-amylase up to 62.23±7.25631% and 63.90±5.632%, respectively. The elevation in the inhibition was observed in the case of their respective silver nanoparticles, such as AgNP seeds and AgNP leaves inhibited the enzyme up to 72.71±7.8569% and 74.04±6.3254%, respectively. They showed lesser cytotoxicity against C2C12 cells. Conclusion: It can be concluded that the leaf and seed extracts of Balanites aegyptiaca and synthesized silver nanoparticles from this plant can be good anti-diabetic agents.

Boosting resistant starch in rice: Bacterial inulin as a metabolic and glucose uptake modulator

Bacillus stercoris PSSR12 (B. stercoris PE), an isolate from rice field soils, was identified via 16s rRNA sequencing. The synthesis of the inulin and inulin producing enzyme (IPE) in B. stercoris PE was verified using SDS-PAGE and FTIR. This study aimed to assess the impact of B. stercoris PE treatment on in vitro inhibition of α-amylase and α-glucosidase from traditional and commercial rice varieties of South India. Additionally, the study investigated enzymatic inhibition and mRNA expression of starch synthesis genes (RAmy1a, GBSSIa, SBEIIa, and SBEIIb). Glucose transporter gene expression (GLUT1 and GLUT4) patterns were analyzed in 3T3-L1 adipocytes to evaluate glucose uptake in B. stercoris PE treated rice varieties. The application of B. stercoris PE enhanced grain quality by imparting starch ultra-structural rigidity, inhibiting starch metabolizing enzymes, and inducing molecular changes in starch synthesis genes. This approach holds promise for managing type II diabetes mellitus and potentially reducing insulin dependence.

Characterization, antioxidant and α-amylase inhibition of polysaccharides and phosphorylated derivatives from finger citron (Citrus medica L. var. sarcodactylis Swingle)

In this study, the structure-activity relationship of finger citron polysaccharides (FCPs) and their phosphorylated derivatives (P-FCPs) was investigated. Three FCPs (FCP20, FCP40 and FCP60) were successively fractionated by ethanol, and were phosphorylated modification to obtain P-FCPs (P-FCP20, P-FCP40 and P-FCP60). FCPs and P-FCPs are acidic heteropolysaccharides composed of mannose, rhamnose, glucose, galactose, arabinose and galacturonic acid, and exhibited different content of neutral sugar, uronic acid, proteins, polyphenols and sulfates. FTIR and NMR analyses determined the structures of FCPs and P-FCPs, indicating that the phosphorylation modification was successful. P-FCPs possessed the smaller molecular weight distribution and particle size, with significant changes in microstructure than FCPs. Additionally, P-FCPs showed significantly increased antioxidant and α-amylase inhibitory activities compared to FCPs. The inhibitory mechanisms of FCP40 and P-FCP40 on α-amylase was a mixed-type manner and dynamic fluorescence quenching. The results demonstrate that phosphorylation modification can alter the structural features and bioactivities of FCPs, providing an approach for the further development of finger citron in the field of medicinal and functional foods.

Antidiabetic Potential and Metabolite Profile of Leaf and Stem Extract of Castanopsis tungurrut (Blume) A.DC.

<p>Diabetes mellitus is a metabolic disorder caused by high blood sugar levels. One species in <em>the Castanopsis</em> genus is proven with a hypoglycemic effect. Therefore, the study aimed to discover the potential of <em>Castanopsis tungurrut</em> as an antidiabetic. Sample extraction, α-amylase inhibition, glucose diffusion analysis, GC-MS analysis, and molecular docking were applied in this study. Maceration of the leaf ethanol extract showed the highest yield value of 21.08%, while the stem extract was 14.04%. Leaf ethanol extract and stem ethyl acetate extract showed the highest inhibiting α-amylase activity with an inhibition value of 33.74%±1.54 and 34.45%±1.08 at 1 mg/mL concentration. The glucose entrapment assay showed that these two extracts could inhibit the diffusion of glucose in the dialysis bag. The final result was glucose concentration in dialysate for the two extracts of 0.114±0.001 mg/mL and 0.116±0.001 mg/mL which was lower than acarbose in 0.120±0.004 mg/mL. GC-MS analysis showed 6 metabolites in leaf ethanol extract and 22 metabolites in stems ethyl acetate extract from an alkane, salicylic, cinnamic, terpene, steroid, and fatty acid. Molecular docking resulting between the compounds with α-amylase enzymes complex showed γ-sitosterol and ß-bisabolene from <em>C. tungurrut</em> extract have the potential to be developed as an antidiabetic drug due to its good inhibitory activity with binding affinity values of -9.1 and -6.9 that considered better and quite close to acarbose as control of -7.7.</p>

In-Vitro Cytotoxic, Hypoglycaemic, and Inhibitory α-Amylase and α-Glucosidase Potential of Flour of Improved Hull-Less and Hulled Barley Varieties.

In-Vitro Cytotoxic, Hypoglycaemic, and Inhibitory α-Amylase and α-Glucosidase Potential of Flour of Improved Hull-Less and Hulled Barley Varieties.

Phytochemicals and enzymes inhibitory potentials of leaves and rootbarks of Sarcocephallus latifolius (smith): In vitro and in silico investigations

In this study, bioactive compounds were isolated and characterized from the leaves and root-barks extracts of S.latifolius, with subsequent in vitro experimental investigations for antihyperglycemic potentials on α-amylase and α-glucosidase enzymes. Thirteen bioactive compounds were identified, including 10-Hydroxystrictosamide (2) and Quinovic acid-3-O-α-L-rhamnosyl-28-O-β-d-glucopyranosyl ester (8), using chromatographic, nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS) techniques. Experimental assays revealed that compounds 1–4 exhibited potent inhibition of α-amylase and α-glucosidase, with compound 2 demonstrating the most potent α-amylase inhibition (IC50 value of 0.52 ± 0.003 μg/mL). Compound 8 showed a lower IC50 value (0.098 ± 0.016 μg/mL) against α-glucosidase compared to compound 2 and acarbose. Synergistic effects among the compounds could enhance their inhibitory actions on the enzymes, positioning them as potential anti-hyperglycemia agents. Compound 2 displayed the highest binding affinity (−7.970 kcal/mol) when docked against α-amylase (PDB ID: 2QV4), comparable to acarbose (−8.515 kcal/mol). It also ranked among the top ligands against α-glucosidase (PDB ID 3TOP), although compound 13 and acarbose had higher docking scores. All compounds exhibited ideal ADMET properties, suggesting good bioavailability and low toxicity. In conclusion, the isolated compounds exhibit promising antihyperglycemic potential and favourable safety profiles for further exploration.

Antioxidant, antidiabetic, and anti-inflammatory activities of flavonoid-rich fractions of Solanum anguivi Lam. fruit: In vitro and ex vivo studies

Diabetes mellitus is a major, rapidly growing endocrine disorder in most countries. The high cost and side effects of conventional drugs for the management of this disease have shifted attention to medicinal plants. Solanum anguivi (S. anguivi) fruits has been reported to be a very good and rich source of polyphenols such as flavonoids, that can be exploited. Flavonoids are plant secondary metabolites widely found in vegetables, fruits and seeds and are known to be of medicinal significance in different range of diseases like diabetes. This study involved in vitro and ex vivo assays on the antioxidant, anti-inflammatory, and antidiabetic properties of flavonoid-rich fractions of S. anguivi fruits. Healthy male Wistar rats (n = 5) weighing 150–180 g were used for ex vivo antioxidant and antidiabetic studies, their liver was exercised for the experiment. The percentage yields of the three flavonoid-rich fractions (Fr. A, B, and C) of S. anguivi fruits obtained from the column chromatographic technique were 15.53 ± 0.75, 11.53 ± 0.80, and 10.17 ± 0.49 mg/g quercetin equivalents. The three fractions (A, B, and C) of S. anguivi fruits significantly scavenged both 2,2-diphenyl-1-picrylhydrazyl (DPPH) with fraction A having the lowest IC50 value (26.14 ± 1.06 μg/ml) compared with fraction B (37.78 ± 5.12 μg/ml) and fraction C (38.24 ± 2.40 μg/ml) when compared with ascorbic acid with the least IC50 value (15.27 ± 0.34 μg/ml). While fraction A (19.61 ± 1.19 μg/ml) scavenged nitric oxide (NO) radicals better than fraction B (22.97 ± 0.55 μg/ml) and fraction C (49.95 ± 6.18 μg/ml). Although ascorbic acid had better scavenging ability than the three fractions (17.23 ± 0.16 μg/ml). The flavonoid-rich fraction A shows better result in inhibiting α-glucosidase with IC50 value of 16.24 μg/ml compared to fraction B (128.04 μg/ml) and fraction C (143.16 μg/ml). For α-amylase, flavonoid-rich fraction A had an IC50 of 31.50 μg/ml compared to B (84.32 μg/ml) and C (145.40 μg/ml). The various controls also showed promising results with acarbose having IC50 of 3.93 μg/mL and 15.66 μg/mL respectively for α-glucosidase and α-amylase. Our findings also showed that FeSO4-induced tissue damage decreased the levels of GSH, SOD, and CAT activities while increasing the levels of MDA. In contrast, following treatment with the three flavonoid fractions of S. anguivi fruits helped to restore these parameters to near-normal levels, by significantly increasing the potential of GSH, SOD, CAT and reducing the levels of MDA which signifies that flavonoid-rich fractions of S. anguivi have great potential to address complications arising from oxidative stress. In addition, the three flavonoid-rich fractions A, B, and C of S. anguivi fruits exhibited ex vivo anti-inflammatory properties via reduced nitric oxide levels in iron-induced oxidative damage. Data obtained from this study shows that the flavonoid-rich fraction of S. anguivi possess anti-diabetic property via inhibition of α-glucosidase and α-amylase and antioxidant property via free radical scavenging. Also, comparing all the fractions, flavonoid-rich fraction A appears to be more potent compared to the fractions B and C. Further research will be needed in isolating and as well applying the fractions in real life situations in the management of diabetes.

Centrosymmetric homo- and heteroleptic core paddle-wheel copper(II) carboxylates; Syntheses, crystal structures, antioxidant, anticancer and enzyme inhibition activity

Synthesis and characterization of homo- (C5H7N2)2[Cu2(3,5-F2C6H3CH2COO)6] (1) and heteroleptic [Cu2(3,5-F2C6H3CH2COO)4(2-CH3Py)2] (2) core paddle-wheel copper(II) carboxylates is reported in the present work. The characterization was made by spectroscopic techniques, elemental and single crystal XRD analyses. The single crystal XRD analysis revealed a rare homoleptic anionic copper(II) carboxylate complex (1) consisting 2-aminopyridinium counter cations and a neutral heteroleptic copper(II) carboxylate complex (2) consisting 2-methyl pyridine as a co-ligand. The copper ions adopted a distorted square pyramidal geometry in both the paddle-wheel dimeric complexes. To evaluate the biological potency of the synthesized complexes, in vitro antioxidant, enzymes inhibition and anticancer activities were performed. The synthesized complexes have shown overall better biological activity compared to the ligand acid. Complex 2 was the most potent DPPH (IC50 =180.96 ± 9.04 µg/mL) and •OH (IC50 = 189.51 ± 9.33 µg/mL) radicals scavenger, α-amylase (IC50 = 441.86 µg/mL) and acetylcholinesterase (IC50 = 88.62 µg/mL) inhibitor. Furthermore, complex 2 activity against malignant glioma U-87 cell line (IC50 = 21.95 µg/mL) was also highest among the tested compounds. However, complex 1 with an IC50 value of 51.83 µg/mL has shown somewhat better inhibition of the butyrylcholinesterase enzyme compared to the complex 2 (IC50 = 56.36 µg/mL).

Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.

Abstract The hypoglycaemic and hypolipidemic potential of ethanol extract of C. bursa-pastoris (ECbp) in streptozotocin (STZ)-provoked diabetic rats was evaluated, and compounds with their α-amylase and α-glucosidase inhibitory potential were isolated. Acute oral toxicity was evaluated in rats. Streptozotocin (STZ) (50 mg/kg body weight) was injected intraperitoneally into rats for diabetes induction. In diabetic rats, ECbp (0.2 g/kg b.w, p.o.) was administered orally for 21 days, and its outcome on blood glucose levels and body weight was observed on a weekly basis besides lipid profile. Compound isolation from ECbp was performed using column chromatography. Oral feeding of ECbp did not produce any toxic effects or death at a dose of 2,000 mg/kg body weight. A serum glucose reduction trend was observed in rats fed with glucose pre-treated with 200 mg/kg b.w. ECbp also appreciably (p < 0.001, p < 0.01, and p < 0.05) diminished raised blood glucose with decreased blood cholesterol levels and led to increased serum high-density lipoprotein levels in comparison to diabetic control rats. Body weight levels were considerably higher (p < 0.05) in diabetic rats treated with ECbp than in diabetic control rats. Isolation of two terpene derivatives (ECbp-1 and ECbp-2) was performed using ECbp, which exhibits significant α-amylase and α-glucosidase inhibition.

In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae).

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid (1), 3,3',4'-tri-O-methyl ellagic acid-4-O-β-D-xylopyranoside (2), 3,3',4'-tri-O-methyl ellagic acid-4-O-β-D-glucopyranoside (3), 3,3'-di-O-methyl ellagic acid-4-O-β-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1-4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1-5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1-11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol-1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.

Chemical composition and antioxidant, enzyme inhibition and cytoprotective activity of two Antarctic lichens of the genus Psoroma (Pannariaceae)

Lichens contain different types of chemical compounds with multiple biological activities that demonstrate their potential pharmacological use. This research aims to report the metabolomic identification of the ethanolic extracts of P. antarcticum and P. hypnorum, their antioxidant, enzyme inhibitory, and their cytoprotection activity. Sixteen metabolites were identified in P. antarcticum and twelve in P. hypnorum; the extracts reported variable antioxidant activity with IC50 >350 µg/mL in DPPH·, values >18 µmol Trolox/g in ORAC and >40 µmol Trolox/g in FRAP and a phenolic compound content >10 mg GAE/g, as well as significant results in cholinesterases, α-glucosidase, pancreatic lipase, α-amylase, and tyrosinase enzyme inhibition activities with IC50 ranging from 18 to 510 µg/mL, and which were complemented by molecular docking experiments. Both extracts showed improved cytoprotection at the concentrations of 0.5 to 1.0 μg/mL. This study contributes to the knowledge of the chemical diversity of Antarctic lichen extracts and their effectiveness in the evaluation of biological activities related to neurodegenerative diseases and metabolic syndrome.

Phytochemical Profile, Antioxidant, Enzyme Inhibition, Acute Toxicity, In Silico Molecular Docking and Dynamic Analysis of Apis Mellifera Propolis as Antidiabetic Supplement.

This study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti-diabetic activity through inhibition of α-amylase (α-AE), α-glucosidase(α-GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13 mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94 μg/ml). This study found that AMPE displayed promising α-AE and α-GE inhibition through in vitro study. Based on LC-MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α-AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α-GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7-Dihydroxy-1-(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene and 3(3-(3,4-Dihydroxybenzyl)-7-hydroxychroman-4-one as novel inhibitors of α-AE and α-GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100 ns simulations. The in vivo acute toxicity assay reveals AMPE as a practically non-toxic product with an LD50 value of 16,050 mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.