Potent Α-glucosidase Inhibitors Research Articles

Design, synthesis, and in silico studies of quinoline-based-benzo[d]imidazole bearing different acetamide derivatives as potent α-glucosidase inhibitors

In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC50 values in the range of 3.2 ± 0.3–185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.

Anti-Obesity Evaluation of Averrhoa carambola L. Leaves and Assessment of Its Polyphenols as Potential α-Glucosidase Inhibitors.

Averrhoa carambola L. is reported for its anti-obese and anti-diabetic activities. The present study aimed to investigate its aqueous methanol leaf extract (CLL) in vivo anti-obese activity along with the isolation and identification of bioactive compounds and their in vitro α-glucosidase inhibition assessment. CLL improved all obesity complications and exhibited significant activity in an obese rat model. Fourteen compounds, including four flavone glycosides (1–4) and ten dihydrochalcone glycosides (5–12), were isolated and identified using spectroscopic techniques. New compounds identified in planta included (1) apigenin 6-C-(2-deoxy-β-D-galactopyranoside)-7-O-β-D-quinovopyranoside, (8) phloretin 3′-C-(2-O-(E)-cinnamoyl-3-O-β-D-fucopyranosyl-4-O-acetyl)-β-D-fucopyranosyl-6′-O-β-D fucopyranosyl-(1/2)-α-L arabinofuranoside, (11a) phloretin3′-C-(2-O-(E)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside, (11b) phloretin3′-C-(2-O-(Z)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside. Carambolaside M (5), carambolaside Ia (6), carambolaside J (7), carambolaside I (9), carambolaside P (10a), carambolaside O (10b), and carambolaside Q (12), which are reported for the first time from A. carambola L. leaves, whereas luteolin 6-C-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside (2), apigenin 6-C-β-D-galactopyranoside (3), and apigenin 6-C-α-L-rhamnopyranosyl-(1-2)-β-L-fucopyranoside (4) are isolated for the first time from Family. Oxalidaceae. In vitro α-glucosidase inhibitory activity revealed the potential efficacy of flavone glycosides, viz., 1, 2, 3, and 4 as antidiabetic agents. In contrast, dihydrochalcone glycosides (5–11) showed weak activity, except for compound 12, which showed relatively strong activity.

Nutraceutical potential of navel orange peel in diabetes management: The chemical profile, antioxidant, α-glucosidase inhibitory and antiglycation effects of its flavonoids

Oxidative damage, chronic hyperglycemia, and the formation of advanced glycation end products (AGEs) are important risk factors associated closely with diabetes and its complications. In the present study, the antidiabetic potential of navel orange peel was explored for the first time by evaluating the antioxidant, α-glucosidase inhibition, and antiglycation activities of its extracts and individual flavonoids. In total, seventeen flavonoids were identified from the peel extract, of which 5-hydroxy-6,7,3′,4′-tetramethoxyflavone, didymin and sinensetin were the most potent antioxidant, α-glucosidase inhibitor, and glycation inhibitor, respectively. In addition, the structure-activity relationship (SAR) studies of these flavonoids were performed in detail. Moreover, the most potent antidiabetic extract of navel orange peel was quantitatively analyzed by HPLC. The present results support the potent application of orange peel as a nutraceutical resource for diabetes management, and might be beneficial to the orange juice industry by providing useful information on the valorization of orange peel.

Placovinane: 1″β-Ethoxy-6,4′-dimethoxy-3″,3″-dimethyl-1″,2″-dihydropyranoisoflavone, a New Isoflavone Derivative

Isoflavonoids possess a 3-phenylchroman skeleton and are the biologically active secondary metabolites of various plants that are used for different health promoting and restoring effects through a variety of mechanisms. Chromatographic separation of the n-hexane extract from the stems of Placolobium vietnamense led to the isolation of a new isoflavone derivative, placovinane (1), together with four known compounds (2–5). The structures of isolated compounds were identified from their spectroscopic data and by comparison with the literature. All isolated compounds were evaluated for their α-glucosidase inhibition. They all exhibited potent α-glucosidase inhibition with IC50 values ranging from 11.0 to 87.3 µM, which was significantly less than the positive control acarbose (IC50 179 µM). The cytotoxicity of 1 was evaluated against KB, Hep G2, and MCF7 cell lines, and displayed weak cytotoxicity toward KB and Hep G2 cell lines, with the IC50 values of 89.6 and 93.8 μM, respectively.

Characterization of phenolics and discovery of α-glucosidase inhibitors in Artemisia argyi leaves based on ultra-performance liquid chromatography-tandem mass spectrometry and relevance analysis

Artemisia argyi leaves (AAL) has been widely used as herbal medicine and food supplement and in China and other Asian countries. The aim of this work is to qualitative and quantitative characterization of phenolic compounds in AAL and screening of natural product inhibitors of α-glucosidase from AAL. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was employed to rapid and comprehensive identification of phenolic compounds in AAL, and a total of thirty-three phenolic compounds were identified. High performance liquid chromatography with diode array detection (HPLC-DAD) was established and validated to simultaneously determinate ten main bioactive phenolics compounds in different batches of AAL samples. Meanwhile, the inhibitory capacities of different batches of AAL samples on α-glucosidase were evaluated. Then, relevance analysis, including grey relational analysis and Pearson correlation analysis were employed to investigate the correlations between the contents of phenolic compounds and α-glucosidase inhibitory activities, and discover the α-glucosidase inhibitors in AAL. The relevance analysis results indicated that three phenolic compounds, 3-caffeoylquinic acid, 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid could be potential α-glucosidase inhibitors in AAL. Moreover, the α-glucosidase inhibitory activities of the three phenolic compounds were validated by in vitro and in vivo experiments. The possible inhibiting effect of the three phenolic compounds on α-glucosidase was also explored by molecular docking analysis, and the results indicated that the binding of the three α-glucosidase inhibitors to α-glucosidase mainly by hydrogen bonds, hydrophobic forces and ionic bonds. The present research provided a deep insight into phenolic compounds and α-glucosidase inhibitory activities of AAL, and discovered the α-glucosidase inhibitors in AAL.

Molecular Docking Reveals Phytoconstituents of the Methanol Extract from Muntingia calabura as Promising α-Glucosidase Inhibitors

Inhibition of α-glucosidase has been used as a management of type 2 diabetes mellitus, where studies are focused on finding more efficacious and safe drugs. Herein, the research aimed to unveil the potential of phytoconstituents contained in methanol extract of Muntingia calabura leaves in inhibiting α-glucosidase through molecular docking simulation. From a systematic search (Scopus), we found 5 eligible articles and identified 28 phytocompounds. Fisetin, pinostrobin, and rhamnetin identified in M. calabura extract were predicted to have good bioavailability. Finally, fisetin was revealed as the most potential α-glucosidase inhibitor candidate with a binding affinity of -7.5 kcal/mol.

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a–o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a–o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results.

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches.

Based on the diverse pharmacological potency and the structural features of succinimide, this research considered to synthesize succinimide derivatives. Moreover, these compounds were estimated for their biological potential in terms of anti-diabetic, anti-cholinesterase, and anti-oxidant capacities. The compounds were synthesized through Michael addition of various ketones to N-aryl maleimides. Similarly, the MOE software was used for the molecular docking study to explore the binding mode of the potent compounds against different enzymes. In the anti-cholinesterase activity, the compounds MSJ2 and MSJ10 exhibited outstanding activity against acetylcholinesterase (AChE), i.e., 91.90, 93.20%, and against butyrylcholinesterase (BChE), i.e., 97.30, 91.36% inhibitory potentials, respectively. The compounds MSJ9 and MSJ10 exhibited prominent α-glucosidase inhibitory potentials, i.e., 87.63 and 89.37 with IC50 value of 32 and 28.04 μM, respectively. Moreover, the compounds MSJ2 and MSJ10 revealed significant scavenging activity against DPPH free radicals with IC50 values of 2.59 and 2.52, while against ABTS displayed excellent scavenging potential with IC50 values 7.32 and 3.29 μM, respectively. The tentative results are added with molecular docking studies in the active sites of enzymes to predict the theoretical protein-ligand binding modes. Further detailed mechanism-based studies in animal models are essential for the in vivo evaluation of the potent compound.

Flavone-1,2,3-triazole derivatives as potential α-glucosidase inhibitors: Synthesis, enzyme inhibition, kinetic analysis and molecular docking study

α-Glucosidase inhibitors are considered prime therapeutics in the management of type-2 diabetes and are preferred due to their localized action ushered by limited side effects. In this regard, nineteen new flavone-1,2,3-triazole derivatives have been designed and synthesized via utilizing an efficient click reaction protocol, and screened for the inhibition of the α-glucosidase enzyme. The reaction conditions were mild, good yielding and required easy work up. All the synthesized flavone-triazole derivatives were found more active against the yeast α-glucosidase with IC50 values ranging from 24.37 ± 0.55–168.44 ± 0.77 μ M as compared to standard inhibitor acarbose (IC50 = 844.81 ± 0.53 μM). The derivatives with 2,5‑dichloro 9k (IC50 = 24.37 ± 0.55 μM) and 4‑chloro 9d (IC50 = 24.77 ± 0.30 μM) substituent bearing an amide linkage were the most active. In the kinetic study of most active derivatives 9k and 9d, they were found to be mixed and uncompetitive inhibitors, respectively. In molecular docking studies, blind docking of the most active compounds was accomplished to find the interactions between the compounds and α-glucosidase that further confirms the mixed or uncompetitive nature of the inhibitors.

Insilico screening and pharmacokinetic properties of phytoconstituents from Ferula asafoetida H.Karst. (Heeng) as potential inhibitors of α-amylase and α-glucosidase for Type2 Diabetes Mellitus.

Ferula asafoetida H.Karst. commonly known as Heeng in India belong to family Umbelliferae (Apiaceae) and has been known for neuroprotective, antioxidant, antispasmodic, hypotensive, hepatoprotective anthelmintic and antagonistic activities. This study was designed to elucidate the key compounds of asafoetida as potential anti alpha amylase and alpha glucosidase inhibitory role in curing the Type 2 Diabetes Mellites. Based upon the literature survey various compounds of the asafoetida was deduced from the Pubchem and protein structure was deduced from protein data bank. Virtual screening was performed using Pyrx with α- amylase and α- glucosidase. Compounds with highest binding affinity score and 3-d interaction analysis was used to identify the potential inhibitors among various compounds. Pharmacokinetic studies for Drug likeliness and toxicity properties were characterized using SWISS ADME and ADMETSAR webservers. The docking scores, bindging affinity and 3d structure studies showed that Kamolonol, Gummosin, Picealactone B, Farnesiferol A are showing potential anti α- amylase whereas Epi-conferdione, Conferol, Feselol, and Farnesiferol C shows α- glucosidase inhibitory properties. The qualitative structural activity relationship for drug-likeness, pharmacokinetics and carcinogenicity analysis indicates that they are safe as drug molecules as these compounds follows the various parameters such as Lipinski's rule of 5, anti-carcinogenicity etc. This study shows that phytochemicals of F. asafoetida have the potential antidiabetic properties which could be further used to develop into effective antidiabetic drug from a natural resource.

Isolation and Characterisation of Hordatine-Rich Fractions from Brewer’s Spent Grain and Their Biological Activity on α-Glucosidase and Glycogen Phosphorylase α

Hordatines are a characteristic class of secondary metabolites found in barley which have been reported to be present in barley malt, beer and, recently, brewer´s spent grain (BSG). However, little is known about their biological activities such as antioxidative effects in beer or antifungal activity as their main task within the plants. We conducted an in vitro investigation of the activity of hordatines isolated from BSG towards enzymes of glucose metabolism. Hordatine-rich fractions from BSG were prepared by solid-liquid extraction (SLE) with 60% acetone followed by purification and fractionation. The fractions were characterised and investigated for their in vitro inhibitory potential on α-glucosidase and glycogen phosphorylase α (GPα). Both enzymes are relevant within the human glucose metabolism regarding the digestion of carbohydrates as well as the liberation of glucose from the liver. In total, 10 hordatine-rich fractions varying in the composition of different hordatines were separated and analysed by mass spectrometry. Hordatine A, B and C, as well as hydroxylated aglycons and many glycosides, were detected in the fractions. The total hordatine content was analysed by HPLC-DAD using a semi-quantitative approach and ranged from 60.7 ± 3.1 to 259.6 ± 6.1 µg p-coumaric acid equivalents/mg fraction. Regarding the biological activity of fractions, no inhibitory effect on GPα was observed, whereas an inhibitory effect on α-glucosidase was detected (IC50 values: 77.5 ± 6.5–194.1 ± 2.6 µg/mL). Overall, the results confirmed that hordatines are present in BSG in relatively high amounts and provided evidence that they are potent inhibitors of α-glucosidase. Further research is needed to confirm these results and identify the active hordatine structure.

Synthesis, spectroscopic and DFT studies of 5-methyl-1H-pyrazole-3-carbohydrazide N-glycoside as potential anti-diabetic and antioxidant agent

A novel pyrazole-carbohydrazide N-glycoside derivative (SM1) was prepared by condensation of D-glucose with 1H-pyrazole-3-carbohydrazide. The structure of SM1 was identified by FT-IR, 1H-NMR, 13C-NMR, UV–Vis and mass spectrometry. Structures and properties of SM1 in gas phase, methanol and aqueous solution were predicted by using hybrid B3LYP method with the 6–31G* and 6–311++G** basis sets. Considerable correlations were observed among the experimental spectra and the corresponding theoretical ones. Both levels of calculations evidence that the glucose moiety modify the dihedral angles and that the C=O and the N-NH group of pyrazole ring are in a cis position. A high negative solvation energy of SM1 in water is observed (-196.36 kJ/mol). Both methods show changes in volumes with the size of basis sets and with the permittivity of solvent while the dipole moments follow approximately a same tendency. NBO and AIM studies predict high stabilities of SM1 with both methods supported probably by low separations MK charges on N7 and O13 atoms while the low reactivity of SM1 could be explained by the low electrophilicity index ω. Complete vibrational assignments of all vibration modes of SM1 are reported together with the scaled harmonic force constants. Compound SM1 was tested in vitro for their α-glucosidase and α-amylase inhibitory activity and the postprandial glucose level after administration of this compound was measured by using oral starch tolerance test (OSTT). The in vitro antioxidant activities of SM1 were determined by DPPH, ABTS, and H2O2 radical scavenging methods and the total reducing power Fe3+-Fe2+ transformation (FRAP). The results shown that SM1 exhibited a potent α-glucosidase inhibition with IC50 value of 59.75 ± 0.80 µM, compared to acarbose (IC50 = 72.58 ± 0.68 µM). The result of OSTT showed that SM1 caused the reduction of blood glucose by 42% at 60 min in diabetic mice, which also showed its significant hypoglycemic effect. Moreover, the results of antioxidant activities showed that the title compound has potent antioxidant and radical scavenger.

Alpha-glucosidase and Alpha-amylase Inhibition Activity of Avocado Fruit of Nepalese Origin

Background: Diabetes has become a major health problem due to its high prevalence, morbidity, and mortality rate. Reducing postprandial hyperglycemia has become the main target in the treatment of diabetes mellitus. So, developing new drugs with fewer side effects has been a major priority. Objective: The main objective of this study is to investigate total phenolic and flavonoid content, antioxidant activity, α-glucosidase, and α-amylase inhibition activity of Persea Americana Mill (avocado) pulp and seed. Methods: The α-glucosidase and α-amylase inhibition activity were performed using substrates PNPG and CNPG3, respectively. DPPH free radical scavenging assay was used to perform the antioxidant activity. The total phenolic content was estimated using folin-ciocalu’s reagent. Likewise, the aluminium trichloride method was applied to find out the total flavonoid content. Results: The crude methanolic extract of avocado seed revealed potent α-glucosidase inhibition activity with an IC50 1.959±0.93μg/mL followed by the avocado pulp 308±2.36μg/mL. Similarly, the IC50 for the α-amylase inhibition activity of avocado seed was found to be 120.3±1.382μg/mL. In addition, the avocado pulp and seed revealed a significant antioxidant activity with IC50 values of 75.01±0.72μg/mL and 6.445±0.62μg/mL, respectively, compared to the standard quercetin 1.525±0.5μg/mL. The total phenolic content of avocado pulp and the seed was reported as 7.031±2.87 mg of GAE/g, and 142.96±1.589 mg of GAE/g, respectively. Similarly, the total flavonoid content of avocado pulp and the seed was found to be 6.313±1.301 mg of QE/g and 48.696±0.110 mg of GAE/g, respectively. Conclusions: The avocado seed of Nepali origin was found to inhibit the digestive enzyme significantly. These findings indicate that avocado fruit of Nepali origin has the potential to develop as an alternative food therapy for diabetic patients. Further research is required to find out the inhibitor compounds.

Assessment of the α-glucosidase and α-amylase inhibitory potential of Paliurus spina-christi Mill. and its terpenic compounds

Type II diabetes mellitus is a common disease in the world and characterized by hyperglycemia. Prevention of diabetes by reducing hyperglycemia depends on the inhibition of α-amylase and α-glucosidase enzymes. In this study, the antidiabetic profiles of the Paliurus spina-christi Mill. fruit were investigated. The fruit of this species is used as an antidiabetic in folk medicine in Turkey. α-amylase and α-glucosidase inhibitory effect studies were conducted to prove this effect. The n-hexane sub-extract of the methanolic fruit extract (IC50 = 445.7 ± 8.5 µg/mL) showed greater inhibitory activity against α-glucosidase than acarbose (IC50 = 4212.6 ± 130.0 µg/mL), in contrast to its slight/no inhibitory effect on α-amylase. The phytochemical investigation of the n-hexane sub-extract of the P. spina-christi fruit led to the isolation of three triterpenes, namely betulin (1a), betulinic acid (1b), and lupeol (2), and a sterol (β-sitosterol) (3). The structures of compounds 1-3 were further analyzed using extensive 1D- and 2D-NMR, and the results were compared with literature. Betulin (1a), betulinic acid (1b), and lupeol (2) are reported from this species for the first time. All the isolated compounds, especially betulin (1a) and betulinic acid (1b) mixture (IC50 = 248 ± 12 µM) showed higher α-glucosidase inhibitory activity than acarbose (IC50 = 6561 ± 207 µM). As extracts, the compounds were also found to be ineffective against α-amylase. Graphical abstract

Gaining deeper insights into 2,5-disubstituted furan derivatives as potent α-glucosidase inhibitors and discovery of putative targets associated with diabetes diseases using an integrative computational approach

Gaining deeper insights into 2,5-disubstituted furan derivatives as potent α-glucosidase inhibitors and discovery of putative targets associated with diabetes diseases using an integrative computational approach

Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives (3a ∼ 3v) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds 3d, 3f, and 3i exhibited much better inhibitory activity with IC50 values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC50 = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds 3d, 3f, and 3i inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.

Extracts of selected Lamiaceae species as promising antidiabetics: Chemical profiling, in vitro and in silico approach combined with dynamical modeling

Diabetes mellitus has been recognized as one of the most challenging public health problems in the 21st century. The present study aimed to investigate the antidiabetic potential of 18 selected Lamiaceae representatives on yeast α-glucosidase and further translate experimental data into predicted human α-glucosidase inhibition. Since conventional antidiabetic drugs exhibit numerous unavoidable side effects, plant extracts are being increasingly explored as safer alternatives. Plant extracts were prepared by maceration, characterized by liquid chromatography-mass spectrometry (LC-MS), and subjected to in vitro determination of yeast α-glucosidase inhibitory potential, after which the kinetic study of one of the most potent extracts (Mentha × piperita) was performed. Docking simulations were done on both yeast and human α-glucosidase to explore binding modes and energies of the secondary metabolites identified in the examined extracts. Finally, the dynamical model has been constructed (adjR2 = 0.9885) and applied to explore extracts’ inhibition potential onto the human α-glucosidase. The constructed dynamical model revealed, for the first time, that different extracts of Satureja montana represent highly promising candidates for the prevention/treatment of diabetes mellitus. Therefore, the dynamical model described in this study represents a useful tool and a significant advance in the discovery of novel therapeutics with antidiabetic potential in humans.

Ultrasonic-assisted synthesis of amantadine derivatives-in vitro urease and α-glucosidase inhibitory activities, mechanistic, and computational studies

Ultrasonic synthesis of 26 amantadine derivatives, (3-28) including seven new compounds, are reported with significantly reduced synthesis time and increased percentage yield relative to literature data. Evaluation of the urease, and α-glucosidase enzyme inhibitory activities of all amantadine derivatives are being reported here for the first time. Three compounds were found to be potent urease inhibitors (IC50 = 9.32 ± 1.01 µM, to IC50 = 11.32 ± 1.05 µM) as compared to the standard drug acetohydroxamic acid (IC50 = 20.3 ± 0.4 µM). Five compounds were found to be potent inhibitors of α-glucosidase (IC50 = 40.63 ± 1.70, to 50.07 ± 1.73) as compared to standard drug acarbose (IC50 = 875.75 ± 2.08 µM). Kinetic studies were performed to investigate competitive and non-competitive inhibition of α-glucosidase enzymes and mixed type inhibition of urease enzyme. All compounds along with parent drug was checked for their cytotoxicity against human fibroblast (B.J.) cell line. Four compounds were found to be toxic, while the rest were nontoxic.Furthermore, in silico studies were performed to predict the binding interactions of the compounds at the active site of the enzymes. The two most active adamantane analogs against urease are those with m- and o-fluoro substitution due to specific interactions with CME592, HOH1918 and GLN635 (3.04, 2.74, and 3.21 Å). Ortho analogs interact with GLN635 (3.04, 3.10 Å). The two analogs having diflouro and tri flouro methyl group, showed a slight lower activity as compared to the first two compounds. This analysis clearly indicates the importance of position of fluoro group in urease inhibition activity. Similarly, in α-glucosidase inhibitors, three compounds with p-OCH3, ethyl groups, and di-fluoro were found to be the most active inhibitors in excellent agreement with experimental data. This study identifies new analogs with potent α-glucosidase and urease inhibitory activities. and, thus, may be of therapeutic importance.

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches.

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.

In vitro and in silico antioxidant and α-glucosidase inhibitory potential of compounds isolated from Garcinia gaudichaudii

Nine compounds including a new one, garcichaudiic acid (1), were isolated from the bark of G. gaudichaudii and their structures were characterized mainly by 1 D and 2 D NMR experiments. The antioxidant capacity of the isolated compounds was determined using DPPH radical scavenging assay and the anti-hyperglycemic activity was assessed by measuring the inhibitory effect against α-glucosidase. Among them, compound 4 showed higher antioxidant activity than the positive control, ascorbic acid, while both compounds 1 and 7 exhibited more significant α-glucosidase inhibitory activity than the reference drug acarbose. Molecular docking analysis of the bioactive compounds was also performed to examine the binding modes and key interactions with the catalytic site.