Potent Α-glucosidase Inhibitors Research Articles

Novel sulfonyl hydrazide based β-carboline derivatives as potential α-glucosidase inhibitors: design, synthesis, and biological evaluation.

A series of novel sulfonyl hydrazide based β-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC50 values being 2.12 ± 0.33-19.37 ± 1.49μM. Compound SX29 with a para-phenyl (IC50: 2.12 ± 0.33μM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32μM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based β-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.

Design of new α-glucosidase inhibitors based on the bis-4-hydroxycoumarin skeleton: Synthesis, evaluation, and in silico studies

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose.

The screening of α-glucosidase inhibitory peptides from β-conglycinin and hypoglycemic mechanism in HepG2 cells and zebrafish larvae

Inhibition of carbohydrate digestive enzymes is a key focus across diverse fields, given the prominence of α-glucosidase inhibitors as preferred oral hypoglycaemic drugs for diabetes treatment. β-conglycinin is the most abundant functional protein in soy; however, it is unclear whether the peptides produced after its gastrointestinal digestion exhibit α-glucosidase inhibitory properties. Therefore, we examined the α-glucosidase inhibitory potential of soy peptides. Specifically, β-conglycinin was subjected to simulated gastrointestinal digestion by enzymatically cleaving it into 95 peptides with gastric, pancreatic and chymotrypsin enzymes. Eight soybean peptides were selected based on their predicted activity; absorption, distribution, metabolism, excretion and toxicity score; and molecular docking analysis. The results indicated that hydrogen bonding and electrostatic interactions play important roles in inhibiting α-glucosidase, with the tripeptide SGR exhibiting the greatest inhibitory effect (IC50 = 10.57 μg/mL). In vitro studies revealed that SGR markedly improved glucose metabolism disorders in insulin-resistant HepG2 cells without affecting cell viability. Animal experiments revealed that SGR significantly improved blood glucose and decreased maltase activity in type 2 diabetic zebrafish larvae, but it did not result in the death of zebrafish larvae. Transcriptomic analysis revealed that SGR exerts its anti-diabetic and hypoglycaemic effects by attenuating the expression of several genes, including Slc2a1, Hsp70, Cpt2, Serpinf1, Sfrp2 and Ggt1a. These results suggest that SGR is a potential food-borne bioactive peptide for managing diabetes.

Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba.

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A-E, 1-5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro[bicyclo[3.2.1]octane-6,3'-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70-8.27 μM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.

Antidiabetic potentials of crude and purified sulphated polysaccharides isolated from Gracilaria gracilis, a seaweed from South Africa

Over 90 % of all cases of diabetes that have been diagnosed are type 2 diabetes (T2D), a disease exacerbated by an increase in sedentary behaviour, bad eating habits, and obesity. This study investigated the antidiabetic properties of Gracilaria gracilis, using in vitro and ex vivo experimental models. The sulphated polysaccharides (SPs) from crude extracts of the seaweed powder was prepared via hot (100°C) and cold (25°C) aqueous extraction procedures before purification via an anion exchange chromatographic technique. Both the crude and purified extracts were characterised by Fourier-transform infrared spectroscopy (FT-IR), LC-MS analysis, and Nuclear Magnetic Resonance (NMR) spectroscopy. The crude cold-aqueous and purified hot-aqueous SPs from G. gracilis had the strongest α-glucosidase inhibitory effect with IC50 value of 0.15 and 0.07 mg/ml, respectively. The purified cold-aqueous SP was the most potent inhibitor of α-glucosidase with an IC50 value of 0.17 mg/ml. The crude and purified SP-rich extracts inhibited pancreatic lipase (hot aqueous SP = 0.03 mg/ml) activity and effectively stimulated glucose uptake in yeast cells. Moreover, they showed significantly (p < 0.05) better intestinal glucose absorption inhibitory properties at the highest concentration (1 mg/ml) and displayed significantly (p < 0.05) better muscle glucose uptake compared to the commercial antidiabetic drug, metformin, at the same concentration. Overall, the current findings indicate that G. gracilis SPs may inhibit carbohydrate-hydrolysing enzymes, limit the release of simple sugars from the gut whilst effectively stimulating the use of glucose by peripheral tissue thus may be suitable to develop antidiabetic food supplements after further animal and clinical trials.

Synthesis of New Glucose-containing 5-Arylisoxazoles and their Enzyme Inhibitory Activity

Abstract: Carbohydrates are an important group of biomolecules that have received special attention due to their significant role in the design and synthesis of new bioactive compounds. In this study, a new class of 5-arylisoxazole-glucose hybrids was designed and synthesized for evaluation of their inhibitory effects on α-glucosidase, α-amylase, and tyrosinase. The target compounds depicted selective α-glucosidase inhibitory activity over α-amylase, which is an important factor in reducing probable gastrointestinal problems in the treatment of type 2 diabetes. In this respect, compound 9a, possessing the phenylisoxazole group, was found to be the most potent α-glucosidase inhibitor (IC50 = 292.2 ± 0.1 μM) compared to acarbose (IC50 = 750.2 ± 0.1 μM) as the positive control. All compounds were also evaluated for their anti-tyrosinase effect, and among them, compound 9j, containing a fluoroaryl moiety, showed potent activity (IC50 = 50.1 ± 6.3 μM) in comparison to kojic acid (IC50 = 23.6 ± 2.6 μM). Also, docking studies were performed to investigate the probable mode of action, which indicated the construction of important H-bonding interactions between the sugar moiety and the enzyme’s active sites. According to the results, hybrids containing heterocycles attached to glucose can be used to inhibit α-glucosidase.

Synthesis, α-glucosidase inhibitory activity, and molecular dynamic simulation of 6-chloro-2-methoxyacridine linked to triazole derivatives

Α-glucosidase inhibition can be useful in the management of carbohydrate-related diseases, especially type 2 diabetes mellitus. Therefore, in this study, a new series of 6-chloro-2-methoxyacridine bearing different aryl triazole derivatives were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. The most potent derivative in this group was 7h bearing para-fluorine with IC50 values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC50 value = 750.0 ± 10.5 μM). A kinetic study of compound 7h revealed that it is a competitive inhibitor against α-glucosidase. Molecular dynamic simulations of the most potent derivative were also executed and indicated suitable interactions with residues of the enzyme which rationalized the in vitro results.

Parkia javanica Edible Pods Reveal Potential as an Anti-Diabetic Agent: UHPLC-QTOF-MS/MS-Based Chemical Profiling, In Silico, In Vitro, In Vivo, and Oxidative Stress Studies.

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

Star anise (Illicium verum Hook. F.) polysaccharides: Potential therapeutic management for obesity, hypertension, and diabetes

This study explores the extraction of polysaccharides from star anise (Illicium verum Hook. f.) with its anti-obesity, antihypertensive, antidiabetic, and antioxidant properties. The aim is to optimize the extraction conditions of star anise polysaccharides (SAP) utilizing propane alcohols-based deep eutectic solvents and microwave-assisted methods. The optimized conditions resulted in an extraction yield of 5.14%. The characteristics of acidic pectin-like SAP, including high viscosity (44.86 mPa s), high oil-holding capacity (14.39%), a high degree of esterification (72.53%), gel-like properties, highly amorphous, a high galacturonic acid concentration, and a highly branching size polysaccharide structure, significantly contribute to their potent inhibition of pancreatic lipase (86.67%), angiotensin-converting enzyme (73.47%), and α-glucosidase (82.33%) activities as well as to their antioxidant properties of azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS, 34.94%) and ferric ion reducing antioxidant power (FRAP, 0.56 mM FeSO4). Therefore, SAP could be used as a potential therapeutic agent for obesity, hypertension, and diabetes mellitus management.

Ultrasound-assisted synthesis of 4-thiazolidinone Schiff bases and their antioxidant, α-glucosidase, α-amylase inhibition, mode of inhibition and computational studies

AbstractDiabetes mellitus (DM) has become a growing concern to global public health, being at the forefront of acute disorders and causes of mortality across the globe. Clinically approved drugs that are currently being used are faced with severe side effects, consequently necessitating the development of new drugs with no/fewer side effects and improved pharmacological potency. Herein, we report a rapid and efficient synthesis of thiazolidinone Schiff bases (2a-2t) from benzylidenehydrazines and thioglycolic acid under neat conditions through ultra-sonication. All the synthesized compounds were obtained in exceptional yields (89–95%) and confirmed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as High-resolution mass spectrometry (HRMS). The synthesized compounds were then evaluated for their antidiabetic activity through α-glucosidase and α-amylase inhibitory potentials and their antioxidant activity through Nitric Oxide (NO), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and Ferric reducing antioxidant power (FRAP) assays. Among them, 2q (IC50 = 96.63 μM) and 2h (IC50 = 125.27 μM) emerged as the most potent derivatives against α-amylase relative to reference drug acarbose (IC50 = 131.63 µM), respectively. Antioxidant evaluation further revealed that the synthesized derivatives were excellent NO scavengers disclosing 2n (IC50 = 44.95 µM) as the most potent derivative. Moreover, in silico ADME calculations predicted these compounds to have excellent drug-like properties. Kinetic studies disclosed the mode of α-amylase inhibition as competitive while molecular docking studies of the most active derivatives performed into the binding active site of human pancreatic α-amylase enzyme deciphered their ligand-protein interactions that explicated their observed experimental potencies.

Hovedulcates A and B, 2,3-dihydrobenzofuran derivatives isolated from the fruits of Hovenia dulcis Thunb. as potential inhibitors of PTP1B and α-glucosidase

From the fruits of Hovenia dulcis Thunb., two new 2,3-dihydrobenzofuran derivatives, named hovedulcates A and B (14 and 16), as well as 20 known compounds (1–13, 15, and 17–22) were isolated. The structures of the isolated compounds were elucidated through a combination of NMR, HR-MS, and ECD spectroscopy analyses, and reported data in the literature. The inhibitory activities of the isolated compounds (1–22) against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase were assessed. Notably, new compounds 14 and 16 exhibited potent inhibitions of both PTP1B and α-glucosidase. The enzyme kinetics analysis was conducted to understand the inhibition mode and inhibitory constants of compounds 14 and 16 for the inhibition of PTP1B and α-glucosidase. Additionally, molecular docking simulations revealed the binding mechanisms and interactions of these compounds with the target enzymes. Our findings suggest that secondary metabolites from H. dulcis fruits are promising natural product treatments for type 2 diabetes.

Magnetic ligand fishing protocol combined with HPLC-FT-ICR-MS for screening potential α-Glucosidase inhibitors from UCG and in silico analysis

Uremic Clearance Granule (UCG) is a traditional Chinese medicines (TCMs) that has been recognized as potentially effective treatment for diabetic nephropathy (DN). However, the chemical composition and the hypoglycemic ingredients of UCG remain unclear. In this experiment, a magnetic ligand fishing protocol combined with HPLC coupled Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR-MS) technology was developed to screen and identify α-Glucosidase inhibitors from UCG. First, constituents of UCG was identified by HPLC-FT-ICR-MS. Next, α-Glucosidase coated Fe3O4@SiO2@NH2 (Fe3O4@SiO2@NH2@α-Glucosidase) nano composites was synthesized. The essential parameters (concentration of Glutaraldehyde (GA), ratio of Fe3O4@SiO2@NH2 to enzyme, crosslinking time and immobilization time) were optimized to obtain maximum enzyme activity and the performance of immobilized enzyme was compared with that of free enzyme. The α-Glucosidase inhibitory activities were then evaluated using autodock and the 4-Nitrophenyl-α-D-glucopyranoside (pNPG) method. As a result, 142 compounds were identified were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. 20 possible α-Glucosidase activity inhibitory components were identified using HPLC-FT-ICR-MS. Molecular docking and inhibition studies showed that 4 compuunds including Limonexic acid, Sanggenol A, Glabrone, Matrine were more likely to stronger α-Glucosidase inhibitory activities than acarbose. In conclusion, the proposed approach, which combined highly specific screening with HPLC-FT-ICR-MS, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicines (TCMs).

Design, synthesis, in vitro, and in silico anti-α-glucosidase assays of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives as new anti-diabetic agents

In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a–n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.

Design, isolation, synthesis, and mechanistic insight of flavonoids isolated from Beilschmiedia obscura, as potential α-glucosidase inhibitors

Flavonoids based on the flavone 1–3 and a biflavanoid 4 with a flavan nucleus were isolated from Beilschmiedia obscura (Stapf). These compounds which include 5- hydroxy - 7,8-dimethoxyflavanone (5), (2 S,4 R)-5, 6,7-trimethoxyflavan-4-ol (6), beilschmieflavonoid B (7), (2 R,3 S)-5,6,7-trimethoxyflavan-3-ol (8), as well as pipyahyine (9), (E,E)-1,6-bis(4-hydroxy-3-methoxyphenyl) hexa-1,5-diene-3,4-dione (10), β-sitosterol (11), pentadecanoic acid (12), pentadecan-1-ol (13), stearic acid (14) and docosane-1,2,4-triol (15), were evaluated as α-glucosidase inhibitors. The most abundant compound 5, was structurally modified by acetylation to compound 16 and NaBH4 reduction to compound 17 which represent two new derivatives of this compound class. These compounds 5–10, 16–17 including kaempferol 18, and epicatechin 19 were screened for α-glucosidase from Bacillus stearothermophyllus and showed good inhibitory activity with IC50 values = (30.55±0.12, 31.8±0.12, 32.47±0.17, 46.53±0.16, 36.43±0.12, 33, 48±0,12, 32.63±0.11 and 43.31±0.12 µM respectively) compared to acarbose (IC50 = 63.77±0.08 µM) as reference drug. Molecular docking and SAR studies further confirmed the plausible binding interactions between the flavonoids and the enzyme α-glucosidase. The results show that these compounds bind effectively to the active site of the protein X-ray structure 3wy1, which is in accordance of the observed α-glucosidase inhibitory activity.

Discovery of Novel and Selective Schiff Base Inhibitors as a Key for Drug Synthesis, Molecular Docking, and Pharmacological Evaluation.

Diabetes mellitus (DM) is a chronic disorder and still a challenge throughout the world, and therefore the search for safe and effective inhibitors for α-amylase and α-glucosidase is increasing day by day. In this work, we try to carry out the synthesis, modification, and computer-aided results of and biological research on thiadiazole-based Schiff base derivatives and evaluate their in vitro α-amylase and α-glucosidase inhibitory potential (1-15). In the current series, all of the synthesized analogues were shown to have potential inhibitory effects on targeted enzymes. The IC50 values for α-amylase values ranged from 20.10 ± 0.40 to 0.80 ± 0.05 μM, compared with the standard drug acarbose having an IC50 value of 10.30 ± 0.20 μM, while for α-glucosidase, the IC50 values ranged from 20.10 ± 0.50 to 1.20 ± 0.10 μM, compared to acarbose with an IC50 value of 9.80 ± 0.20 μM. For better understanding, a SAR investigation was undertaken. In this series, nine scaffolds (1, 2, 3, 6, 9, 10, 11, 13, and 15) were more active than the reference drug and the docking parameter RMSD values for α-glucosidase and α-amylase were 1.766, 2.7746, 1.6025, 2.2112, 3.5860, 2.3360, 1.6178, 2.0254, and 2.0797 and 2.6020, 1.9509, 3.1642, 1.7547, 2.2130, 1.4221, and 1.1087, respectively. The toxicity of the selected analogues was calculated by using the OSIRIS tool, and the TPSA values were found to be lower than 140 to represent the drug-like properties; those from Molinspiration were studied as well. The following properties were studied and found to have better biological properties. The remaining analogues (4, 5, 7, 8, 12, and 14) were also identified as potential inhibitors of both enzymes, but they were less active than the reference due to the substituents attached to the aromatic parts. The structures of synthesized compounds were confirmed through different spectroscopic analyses.

Antibacterial, antidiabetic and antioxidant bioevaluation of Calamus leptospadix Griff. and isolation of a flavan type compound

The plant based natural products have always been a rich source of bioactive molecules for drug discovery. The tender shoots of Calamus leptospadix Griff., an edible medicinal plant was extracted using methanol, water and ethanol as three different solvents to study the effect of the extracting solvents and temperature on their antioxidant, antidiabetic and antibacterial properties and total phenolic and flavonoid contents. The antioxidant properties were determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assay. The α-glucosidase inhibitory assay was carried out to determine the antidiabetic potential. The antibacterial properties of the extracts were determined against four strains of bacterial species viz. Bacillus subtilis, Streptococcus pneumoniae, Escherichia coli and Citrobacter freundii using Broth macro dilution method.The methanolic extracts of the plant were found to possess the highest total phenolic and total flavonoid contents. In the antioxidant assays, the cold methanolic extract was found to exhibit the highest DDPH radical scavenging activity and ferric-reducing antioxidant power. In the antidiabetic assay, the extract exhibited better α-glucosidase inhibitory potential than that of the positive control acarbose. It was also found to be effective against both gram-positive and gram-negative strains in the antibacterial assay. A flavan-type compound 4-(5,7-dimethoxychroman-2-yl)phenol was isolated from the most bioactive cold methanolic extract of the plant and characterised from its XRD, 1H and 13C NMR, HRMS and IR data.

Substrate Influence on Enzymatic Activity in Cordyceps militaris for Health Applications

Cordyceps militaris, well known for its therapeutic potential in managing type-2 diabetes through the inhibition of α-amylase and α-glucosidase enzymes, was the central focus of this research, which investigated the influence of various cultivation substrates on its enzymatic inhibitory properties and bioactive compound content. Previous studies have primarily focused on the general pharmacological benefits of C. militaris but have not thoroughly explored how different substrates affect its bioactive profile and enzyme inhibitory activities. This study aimed to evaluate the impact of substrate selection on the enzyme inhibition activities and the levels of bioactive compounds such as cordycepin and adenosine in C. militaris, demonstrating that substrate selection markedly affects both these enzymes’ inhibition activities and bioactive compound levels. Particularly, C. militaris fruiting bodies grown on Brihaspa atrostigmella showed the highest concentrations of cordycepin (2.932 mg/g) and adenosine (1.062 mg/g). This substrate also exhibited the most potent α-glucosidase inhibition with an IC50 value of 336.4 ± 16.0 µg/mL and the most effective α-amylase inhibition with an IC50 value of 504.6 ± 4.2 µg/mL. Conversely, C. militaris cultivated on the solid residues of Gryllus bimaculatus displayed the strongest xanthine oxidase (XOD) inhibition, with the lowest IC50 value of 415.7 ± 11.2 µg/mL. These findings highlight the critical role of substrate choice in enhancing the medicinal properties of C. militaris, suggesting that optimized cultivation can enhance the bioactive properties for more effective natural therapies for diabetes and other metabolic disorders. This study not only extends the understanding of C. militaris’ pharmacological potential but also illustrates its applicability in developing customized treatment options.

Green solvent-based extraction of three Fabaceae species: A potential antioxidant, anti-diabetic, and anti-leishmanial agents

The Fabaceae is renowned for its diverse range of chemical compounds with significant biological activities, making it a valuable subject for pharmacological studies. The chemical composition and biological activities of three Fabaceae species were investigated using methanol separately and in combination with dimethyl sulfoxide (DMSO) and glycerol for extraction. The results revealed the highest phenolic (49.59 ± 0.38 mg gallic acid equivalent/g), flavonoid (29.16 ± 0.39 mg rutin equivalent/g), and alkaloid (14.23 ± 0.54 mg atropine equivalent/g) contents in the Caesalpinia decapetala methanol extracts. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and DNA protection activity were the highest (0.88 ± 0.43 μg/mL IC50 and 2149.26 band intensity) in Albizia julibrissin methanol extracts. The α-amylase activity was highest in all methanol extracts (<15 μg/mL IC50 values), while the α-glucosidase inhibition potential was highest (<1 μg/mL IC50 value) in the methanol–glycerol and methanol–DMSO extracts. Pearson coefficient analysis showed a strong positive correlation between the DPPH and α-amylase assays and phytochemicals. Anti-leishmanial activity was observed in decreasing order: A. julibrissin (74.75 %) > C. decapetala (70.86 %) > Indigofera atropurpurea (65.34 %). Gas chromatography-mass spectrometry revealed 33 volatile compounds and, aamong these (Z)-9-octadecenamide was detected in the highest concentration ranging from 21.85 to 38.61 %. Only the methanol extracts of the examined species could be assessed for in vivo studies for immediate applications.

Synthesis, in vitro α-glucosidase inhibitory potential and in silico study of 2‑chloro pyridine incorporated thiosemicarbazones

Diabetes is a devastating metabolic illness that affects people of all ages and is widespread around the world as a result of the malfunctioning of prior treatment approaches. This work attempts to treat type 2 diabetes mellitus (T2DM) by outlining the design, synthesis, in vitro and in silico assessment of 2-Nicotinaldehyde-based thiosemicarbazones as possible inhibitors of α-glucosidase. The synthesized derivatives 3(a-m) displayed excellent to good inhibitory potential against standard drug acarbose (IC50 = 4.10 ± 0.16 µM to 32.76 ± 0.80 µM. Among these compounds 3m displayed highest inhibition activity with IC50 value of 4.10 ± 0.16 µM. SAR of the derivatives have shown that the compounds with meta substitution displayed better activity than the para substitution. In order to obtain more profound understanding, molecular dynamics, and in silico molecular docking simulations were performed to examine the interactions, stability, orientation, and conformation of the synthesized derivatives inside the α-glucosidase active pocket.

Identification of Potential α-Glucosidase Inhibitors from American Ginseng Processed Products by UHPLC-Q-Orbitrap/MS and Molecular Docking

Identification of Potential α-Glucosidase Inhibitors from American Ginseng Processed Products by UHPLC-Q-Orbitrap/MS and Molecular Docking