Potent Α-glucosidase Inhibitory Activity Research Articles

Undescribed Cyclohexene and Benzofuran Alkenyl Derivatives from Choerospondias axillaris, a Potential Hypoglycemic Fruit.

The fruit of Choerospondias axillaris (Anacardiaceae), known as south wild jujube in China, has been consumed widely in several regions of the world to produce fruit pastille and leathers, juice, jam, and candy. A comprehensive chemical study on the fresh fruits led to the isolation and identification of 18 compounds, including 7 new (1-7) and 11 known (8-18) comprised of 5 alkenyl (cyclohexenols and cyclohexenones) derivatives (1-5), 3 benzofuran derivatives (6-8), 6 flavonoids (9-14) and 4 lignans (15-18). Their structures were elucidated by extensive spectroscopic analysis. The known lignans 15-18 were isolated from the genus Choerospondias for the first time. Most of the isolates exhibited significant inhibitory activity on α-glucosidase with IC50 values from 2.26 ± 0.06 to 43.9 ± 0.96 μM. Molecular docking experiments strongly supported the potent α-glucosidase inhibitory activity. The results indicated that C. axillaris fruits could be an excellent source of functional foods that acquire potential hypoglycemic bioactive components.

Dauresorcinols A and B, two pairs of merosesquiterpenoid enantiomers with new carbon skeletons from Rhododendron dauricum

Five pairs of new merosesquiterpenoid enantiomers, named dauresorcinols A−E (1−5), were isolated from the leaves of Rhododendron dauricum. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum chemical calculations, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis. Dauresorcinols A (1) and B (2) possess two new merosesquiterpene skeletons bearing an unprecedented 2,6,7,10,14-pentamethyl-11-oxatetracyclo[8.8.0.02,7.012,17]octadecane and a caged 15-isohexyl-1,5,15-trimethyl-2,10-dioxatetracyclo[7.4.1.111,14.03,8]pentadecane motif, respectively. Plausible biosynthetic pathways of 1−5 are proposed involving key oxa-electrocyclization and Wagner−Meerwein rearrangement reactions. (+)/(−)-1 and 3−5 showed potent α-glucosidase inhibitory activity, 3 to 22 times stronger than acarbose, an antidiabetic drug targeting α-glucosidase. Docking results provide a basis to design and develop merosesquiterpenoids as potent α-glycosidase inhibitors.

Phenolic constituents with potent α-glucosidase inhibitory and cytotoxic activities from Rumex nepalensis var. remotiflorus

Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-β-D-glucoside-6′-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4–5, and 7–9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 μM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 μM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.

Exploring Astrodaucus orientalis (L.) Drude: Phytochemical Analysis and its Biological Potential Against Alzheimer's and Diabetes.

In current study antioxidant, antidiabetic, antimicrobial, anticholinesterase, and human carbonic anhydrase I, and II (hCA I and II) isoenzymes inhibition activities of Astrodaucus orientalis different parts were investigated. Achetylcholinesterse (AChE) and butyrylcholinesterse (BChE) inhibitory activities of octyl acetate were determined via molecular docking. Quantitative assessment of specific secondary metabolites was conducted using LC-MS/MS. An examination of chemical composition of essential oils was carried out by GC-MS/MS. A thorough exploration of plant's anatomical characteristics was undertaken. The highest phenolics level and DPPH antioxidant capacity were seen in root and fruit. Fruit essential oil demonstrated the highest AChE inhibition (44.13±3.61 %), while root dichloromethane sub-extract had the best inhibition towards BChE (86.13±2.58 %). Cytosolic hCA I, and II isoenzymes were influentially inhibited by root oil with 1.974 and 2.207 μM IC50 values, respectively. The most effective extracts were found to be root all extract/sub-extracts (except water) against C. tropicalis and C. krusei strains with MIC value 160>μg/mL. Sabinene (29.4 %), α-pinene (20.2 %); octyl acetate (54.3 %); myrcene (28.0 %); octyl octanoate (71.3 %) were found principal components of aerial parts, roots, flowers, and fruits, respectively. Flower essential oil, fruit dicloromethane and ethyl acetate exhibited potent α-glucosidase inhibitory activity with 900, 40, and 937 μg/mL IC50 values, respectively.

Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes

Abstract A synthesized Schiff base ligand 4-{(Z)-[(2-hydroxy-1-naphthyl)methylene]amino}-4-antipyrene (H-NAPP) was confirmed by single crystal diffraction analysis. The H-NAPP was crystalized in the P 21 21 21 space group and orthorhombic crystal system. The Schiff base ligand H-NAPP bears potential donor sites and therefore it was reacted with transition metal ions Co2+, Ni2+, Cu2+, and Zn2+ to yield respective metal complexes. All reaction products were investigated by elemental analyses and IR spectroscopic techniques. The combined spectroscopic characterizations revealed the distorted square planar geometries for all the synthesized metal complexes. The metal complexes were further studied for their thermal stabilities using TG techniques and proved to be thermally cleaved in the temperature range of 30–1,000°C in air. Pseudo-mirrored 2D fingerprint plots were used for the short interatomic interactions in the crystal structure. The major short interatomic interactions involve the hydrogen bonding which covers the Hirshfeld surfaces {H···H, O···H and C···H}. The ligand and complexes were investigated for a potential α-glucosidase inhibitory activity. While relatively inactive throughout, some notable differences were observed and, surprisingly, the ligand was found to be more active than its complexes.

Structure-yeast α-glucosidase inhibitory activity relationship of 9-O-berberrubine carboxylates.

Thirty-five 9-O-berberrubine carboxylate derivatives were synthesized and evaluated for yeast α-glucosidase inhibitory activity. All compounds demonstrated better inhibitory activities than the parent compounds berberine (BBR) and berberrubine (BBRB), and a positive control, acarbose. The structure-activity correlation study indicated that most of the substituents on the benzoate moiety such as methoxy, hydroxy, methylenedioxy, benzyloxy, halogen, trifluoromethyl, nitro and alkyl can contribute to the activities except multi-methoxy, fluoro and cyano. In addition, replacing benzoate with naphthoate, cinnamate, piperate or diphenylacetate also led to an increase in inhibitory activities except with phenyl acetate. 9, 26, 27, 28 and 33 exhibited the most potent α-glucosidase inhibitory activities with the IC50 values in the range of 1.61-2.67μM. Kinetic study revealed that 9, 26, 28 and 33 interacted with the enzyme via competitive mode. These four compounds were also proved to be not cytotoxic at their IC50 values. The competitive inhibition mechanism of these four compounds against yeast α-glucosidase was investigated using molecular docking and molecular dynamics simulations. The binding free energy calculations suggest that 26 exhibited the strongest binding affinity, and its binding stability is supported by hydrophobic interactions with D68, F157, F158 and F177. Therefore, 9, 26, 28 and 33 would be promising candidates for further studies of antidiabetic activity.

Effect of Phenolics from Aeonium arboreum on Alpha Glucosidase, Pancreatic Lipase, and Oxidative Stress; a Bio-Guided Approach.

Metabolic syndrome (MetS) is a global issue affecting over a billion people, raising the risk of diabetes, cardiovascular disorders, and other ailments. It is often characterized by hypertension, dyslipidemia and/or obesity, and hyperglycemia. Chemical investigation of Aeonium arboreum (L.) Webb & Berthel led to the isolation of six compounds, viz. β-sitosterol, β-sitosterol glucoside, myricetin galactoside, quercetin rhamnoside, kaempferol rhamnoside, and myricetin glucoside. Interestingly, A. arboreum's dichloromethane (DCM), 100 and 50% MeOH Diaion fractions and the isolated compound (quercetin-3-rhamnoside) revealed potent α-glucosidase inhibitory activity, especially 50% Diaion fraction. In addition, they also showed very potent antioxidant potential, especially the polar fractions, using DPPH, ABTS, FRAP, ORAC, and metal chelation assays. Notably, the 50% Diaion fraction had the highest antioxidant potential using DPPH and ORAC assays, while the 100% Diaion fraction and quercetin-3-rhamnoside showed the highest activity using ABTS, FRAP, and metal chelation assays. Also, quercetin-3-rhamnoside showed a good docking score of -5.82 kcal/mol in comparison to acarbose. In addition, molecular dynamic stimulation studies illustrated high stability of compound binding to pocket of protein. Such potent activities present A. arboreum as a complementary safe approach for the management of diabetes mellitus as well as MetS.

Synthesis of novel coumarin-based thiosemicarbazones and their implications in diabetic management via in-vitro and in-silico approaches

Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a–3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.

Chemical Composition, Anti-α-Glucosidase Activity, and Molecular Modelling Studies of Cleistocalyx operculatus Essential Oil

In this study, chemical components, α-glucosidase inhibitory activities, and molecular modelling studies of the essential oil extracted from the Cleistocalyx operculatus leaves were investigated. In total, thirty compounds were identified using GC/MS, representing 98.3% of the oil. Of these, the two most dominant constituents of the essential oil were determined as (Z)-β-ocimene (30.4%) and allo-ocimene (31.6%). The α-glucosidase inhibitory experiments indicated that the essential oil exhibited potent α-glucosidase inhibitory activities, with IC50 values of 61.82 ± 3.91 µg/mL. For further investigation into inhibitory mechanisms, molecular docking simulations were performed to investigate structural interactions between two dominant constituents and the α-glucosidase protein. The simulation revealed that allo-ocimene (31.6%) and (Z)-β-ocimene (30.4%) have protein binding affinities of −5.358 and −5.330 kcal/mol, respectively. Moreover, molecular dynamic simulation indicated that the complexes of two compounds and the target protein were stable over 100 ns. Overall, these findings suggest that the essential oil of C. operculatus leaves could be a natural source of potential α-glucosidase inhibitors.

Diphenyl-substituted triazine derivatives: synthesis, α-glucosidase inhibitory activity, kineticsand in silico studies.

Background: Diabetes mellitus (DM) is a chronic disorder, considered to be a major global health challenge in the 21st century. α-Glucosidase enzyme is a well-known drug target to treat Type II DM. Methods: A new library of biphenyl-substituted triazines was synthesized and confirmed by various spectroscopic techniques. Results: All compounds showed potent α-glucosidase inhibitory activity, with IC50 values ranging from 35.35±0.34 to 564.41±0.91μM, as the standard acarbose, IC50 value of 750.7±0.13μM. Our in silico study has predicted key interactions with the enzyme's active site. Drug-likeness and absorption, distribution, metabolism, excretionand toxicitywere also studied. Conclusion: This study has identified a range of potential hits against theα-glucosidase enzyme that may serve as antidiabetic agents after further investigations.

Triazolothiadiazoles and triazolothiadiazines as potent α-glucosidase inhibitors: Mechanistic insights from kinetics studies, molecular docking and dynamics simulations

Diabetes mellitus has been considered as a serious health problem worldwide due its high prevalence rate and associated complications. In this context, the current research work aims at exploring new structural leads for the treatment of a major metabolic disorder, diabetes mellitus type 2. The outcomes of our prior studies on a diverse set of triazolothiadiazole and triazolothiadiazine derivatives and their therapeutic potential, encouraged us to explore their anti-diabetic competency by targeting the key carbohydrate catabolic enzyme, α-glucosidase. Therefore, all these analogues were examined to reveal their contribution towards this severe metabolic issue. Interestingly, all the tested compounds (2a-2l and 3a-3p) exhibited several times more potent α-glucosidase inhibitory activities (IC50 in the range of 2.44–219.93 μM) as compared to marketed drug, acarbose (IC50 = 873.34 ± 1.67 μM). Furthermore, their mechanism of action was investigated through in vitro kinetics studies which revealed compounds 3a, 3d, 3o, and 2k as competitive inhibitors, and 3f as a mixed type inhibitor of α-glucosidase. In addition, in silico molecular docking and molecular dynamics simulations were applied to observe the mode of interaction of the active hits within the binding pocket of α-glucosidase. Both docking and simulation results favored our in vitro mechanistic analysis.

Design, synthesis, in vitro anti-α-glucosidase evaluations, and computational studies of new phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides as potential anti-diabetic agents

An important target in the treatment of type 2 diabetes is α-glucosidase. Inhibition of this enzyme led to delay in glucose absorption and decrease in postprandial hyperglycemia. A new series of phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides 11a–n were designed based on the reported potent α-glucosidase inhibitors. These compounds were synthesized and screened for their in vitro inhibitory activity against the latter enzyme. The majority of the evaluated compounds displayed high inhibition effects (IC50 values in the range of 45.26 ± 0.03–491.68 ± 0.11 µM) as compared to the positive control acarbose (IC50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC50 values of 45.26 ± 0.03 and 46.25 ± 0.89 µM. Kinetic analysis revealed that the compound 11j is a competitive inhibitor with a Ki of 50.4 µM. Furthermore, the binding interactions of the most potent compounds in α-glucosidase active site were studied through molecular docking and molecular dynamics. The latter studies confirmed the obtained results through in vitro experiments. Furthermore, in silico pharmacokinetic study of the most potent compounds was also performed.

Evaluation of alpha-glucosidase inhibition activity and glycosides in the Syringa pubescens Turcz from different geographical origin

Inhibition of α-glucosidase is an attractive strategy for the control of hyperglycaemia. Naturally occurring bioactive compounds are potential sources of α-glucosidase inhibitors. The Syringa pubescens Turcz (SP) is commonly used as Chinese folk medicine for treatment of hepatitis and cirrhosis. However, the anti-hyperglycemic activity of SP was lack of study and the report on compounds of α-glucosidase inhibitory activity of SP was also insufficient. In this study, the α-glucosidase inhibitory activity of SP extract was firstly assessed in vitro. The quantification analysis of bioactive glycosides in SP collected at different geographical origins and its correlation with α-glucosidase inhibitory activities were investigated. As the results, six glycosides including salidroside, echinacoisde, forsythoside B, verbascoside, isoacteoside and oleuropein were simultaneously determined using HPLC-DAD method. Moreover, SP collected from different geographical origins exhibited different concentrations of bioactive glycosides and had potential α-glucosidase inhibitory activity. The results of correlation analysis indicated that the amounts of glycosides were positively correlated with the α-glucosidase inhibitory activities of SP. Then, the evaluation of α-glucosidase inhibitory activity of six glycosides was performed. And docking study was conducted to predict the possible binding sites of forsythoside B. Forsythoside B might be the most possible α-glucosidase inhibitor in SP.

One undescribed glycoside benzofuran derivative and a new p-hydroxybenzoate glycoside from the leaves of Illicium dunnianum Tutcher

One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3–8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 μM), compounds 1–8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380–655 μM.

Antidiabetic and antioxidant activities of Mitragyna speciosa (kratom) leaf extract in type 2 diabetic rats

Mitragyna speciosa is a medicinal plant with a reputation for treating pains, diabetes as well as increasing energy and sexual desires. However, there is no scientific evidence to validate the antidiabetic effect of M. speciosa. This study investigated the antidiabetic effects of M. speciosa (Krat) ethanolic extract on fructose and streptozocin (STZ)-induced type 2 diabetic rats. In vitro antioxidant and antidiabetic effects were evaluated using DPPH, ABST, FRAP and α-glucosidase inhibitory assays. Rats with fructose/STZ induced T2D were treated with Krat (100 and 400 mg/kg) or metformin (200 mg/kg) for 5 weeks via oral gavage. Krat showed good antioxidant activity and also displayed potent α-glucosidase inhibitory activity. Administration of Krat to the diabetic rats significantly improved body weight gain, restored alterations in blood glucose level, glucose tolerance, dyslipidemia (increased cholesterol, triglycerides, low-density lipoprotein-cholesterol and reduced high-density lipoprotein), hepatorenal biomarkers alterations (alanine transaminase, aspartate transaminase, alanine phosphatase, creatinine and blood urea nitrogen) and oxidative stress indices (superoxide dismutase, glutathione and malondialdehyde)in the treated diabetic rats. Furthermore, Krat also restored pancreatic histological and increased immunohistochemical aberrations in the diabetic rats. These results for the first time demonstrated the antidiabetic and antihyperlipidemic potentials of M. speciosa, thus providing scientific reinforcement for the traditional use of the plant in the treatment of diabetes.

New β-carboline derivatives as potential α-glucosidase inhibitor: Synthesis and biological activity evaluation

α-Glucosidase is an important therapeutic target of diabetes mellitus. To find potent α-glucosidase inhibitors, thirty-one β-carboline derivatives containing piperazine moieties (6a∼6u, 7a∼7j) were synthesized and evaluated their α-glucosidase inhibitory activity. Most β-carboline derivatives showed potential α-glucosidase inhibitory activity, especially, compound 7c presented obvious α-glucosidase inhibitory activity (IC50: 8.9 ± 0.2 μM), ∼ 69 folds stronger than acarbose (IC50: 610.7 ± 0.1 μM). Inhibition mechanism and kinetics explained compound 7c to be a reversible and mixed-type inhibitor. CD spectra, 3D fluorescence, and molecular docking were employed to reveal the mechanisms of 7c against α-glucosidase. Cell cytotoxicity assay ascertained low cytotoxicity of 7c.

Characterization of Antioxidant and α-Glucosidase Inhibitory Compounds of Cratoxylum formosum ssp. pruniflorum and Optimization of Extraction Condition.

Cratoxylum formosum ssp. pruniflorum (Kurz.) Gogel (Guttiferae), called kuding tea, is widely distributed in Southeast Asia. In this study, the constituents and biological activity of C. formosum ssp. pruniflorum were investigated. Extract of its leaves, roots and stems showed antioxidant and α-glucosidase inhibitory activity. Interestingly, comparison of the metabolite profiles of leaves, roots and stems of C. formosum ssp. pruniflorum by LC-MS analysis showed a great difference between the roots and leaves, whereas the roots and stems were quite similar. Purification of the roots and leaves of C. formosum ssp. pruniflorum through various chromatographic techniques resulted in the isolation of 25 compounds. The structures of isolated compounds were elucidated on the basis of spectroscopic analysis as 18 xanthones, 5 flavonoids, a benzophenone and a phenolic compound. Among them, a xanthone (16) and a benzophenone (19) were first reported from nature. Evaluation of biological activity revealed that xanthones had a potent α-glucosidase inhibitory activity, while flavonoids were responsible for the antioxidant activity. To maximize the biological activity, yield and total phenolic content of C. formosum ssp. pruniflorum, extraction conditions such as extraction solvent, time and temperature were optimized using response surface methodology with Box-Behnken Design (BBD). Regression analysis showed a good fit of the experimental data, and the optimal condition was obtained as MeOH concentration in EtOAc, 88.1%; extraction time, 6.02 h; and extraction temperature 60.0 °C. α-Glucosidase inhibitory activity, yield and total phenolic content under the optimal condition were found to be 72.2% inhibition, 10.3% and 163.9 mg GAE/g extract, respectively. These results provide useful information about C. formosum ssp. pruniflorum as functional foods for oxidative stress-related metabolic diseases.

Antioxidant, antimicrobial, and α-glucosidase inhibitory activities of saponin extracts from walnut (Juglans regia L.) leaves

Objective: To investigate the relationship between triterpenoid saponin content and antioxidant, antimicrobial, and α-glucosidase inhibitory activities of 70% ethanolic, butanolic, aqueous, supernate and precipitate extracts of Juglans regia leaves.Methods: Triterpenoid saponins of different Juglans regia leaf extracts were measured by the vanillin method. Antioxidant activity was evaluated against DPPH and ABTS free radicals. We also assessed α-glucosidase inhibitory and antimicrobial activities of the leaf extracts. Pearson's correlation coefficient was evaluated to determine the correlation between the saponin content and biological activities.Results: The butanolic extract was most effective against DPPH with an IC50 of 6.63 μg/mL, while the aqueous extract showed the highest scavenging activity against ABTS free radical with an IC50 of 42.27 μg/mL. Pearson's correlation analysis indicated a strong negative correlation (r = -0.956) between DPPH radical scavenging activity (IC50) and the saponin content in the samples examined. In addition, the aqueous extract showed the best α-glucosidase inhibitory activity compared with other extracts. All the extracts had fair antibacterial activity against Bacillus subtilis, Escherichia coli, and Klebsiella pneumoniae except for the aqueous extract.Conclusions: Juglans regia extracts show potent antioxidant, antimicrobial, and α-glucosidase inhibitory activities. There is a correlation between saponin levels in Juglans regia leaf extracts and the studied activities. However, additional research is required to establish these relationships by identifying the specific saponin molecules responsible for these activities and elucidating their mechanisms of action.

Two new phenylbutenoids from the rhizomes of cassumunar ginger and their α-glucosidase inhibitory activity

An extract from the rhizomes of Cassumunar ginger (Zingiber purpureum Roscoe). was found to have significant α-glucosidase inhibitory activity with an IC50 value of 6.3 µg/mL. Two new phenylbutenoids, cassudimin A (1) and cassumunol N (2), and seven known compounds (3–9) were isolated. Their structures and relative configurations of two new compounds were elucidated based on spectra interpretation. Compounds 1–3, 6–9 showed more potent α-glucosidase inhibitory activity than a positive control, acarbose (IC50 = 168.0 µM). Dehydrozingerone (6) exhibited the most potent α-glucosidase inhibition with an IC50 value of 8.3 μM. Compounds 7 and 9 were found in Z. purpureum rhizomes for the first time.

Synthesis, biological evaluation and molecular docking studies of chromone derivatives as potential α-glucosidase inhibitors

A series of chromone derivatives were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity by using in vitro methods and molecular docking studies. Some new synthetic compounds showed excellent α-glucosidase inhibitory activity with IC50 values in the range from 10.9 ± 0.29 to 146.50 ± 0.49 µM. Among them, compound 6m exhibited the most potent α-glucosidase inhibitory activity with an IC50 value of 10.9 ± 0.29 μM. Enzyme kinetic study demonstrated that 6m was a mixed-type inhibitor (Ki = 16.87 μM). Circular dichroism spectra and fluorescence quenching experiments further confirmed that the secondary structure of α-glucosidase was changed by the binding of 6m. Molecular docking studies showed that the aryl groups of 6m interactions with the residues Tyr-71, Phe-157, Phe-177, and Phe-300 formed the CH-π. Cell viability assay has shown that 6m exhibited low cytotoxic activity against human normal cell lines.