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Fish discards and by-products can be transformed into high value-added products such as fish protein hydrolysates (FPH) containing bioactive peptides. Protein hydrolysates were prepared from different parts (whole fish, skin and head) of several discarded species of the North-West Spain fishing fleet using Alcalase. All hydrolysates had moisture and ash contents lower than 10% and 15%, respectively. The fat content of FPH varied between 1.5% and 9.4% and had high protein content (69.8–76.6%). The amino acids profiles of FPH are quite similar and the most abundant amino acids were glutamic and aspartic acids. All FPH exhibited antioxidant activity and those obtained from Atlantic horse mackerel heads presented the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, reducing power and Cu2+ chelating activity. On the other hand, hydrolysates from gurnard heads showed the highest ABTS radical scavenging activity and Fe2+ chelating activity. In what concerns the α-amylase inhibitory activity, the IC50 values recorded for FPH ranged between 5.70 and 84.37 mg/mL for blue whiting heads and whole Atlantic horse mackerel, respectively. α-Glucosidase inhibitory activity of FPH was relatively low but all FPH had high Angiotensin Converting Enzyme (ACE) inhibitory activity. Considering the biological activities, these FPH are potential natural additives for functional foods or nutraceuticals.

Diabetes mellitus, particularly type 2 diabetes, is a growing global health challenge characterized by chronic hyperglycemia due to insulin resistance. One therapeutic approach to managing this condition is the inhibition of α-glucosidase, an enzyme involved in carbohydrate digestion, to reduce postprandial blood glucose levels. In this study, a series of thiosemicarbazide-linked quinoline-piperazine derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity, to identify new agents for type 2 diabetes management. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the aryl ring significantly impacted the inhibitory potency. Among the synthesized derivatives, the 2,5-dimethoxy phenyl substitution ( 7j ) exhibited the most potent activity with an IC 50 value of 50.0 µM, demonstrating a 15-fold improvement compared to the standard drug acarbose. Kinetic studies identified compound 7j as a competitive inhibitor, with a K i value of 32 µM. Molecular docking simulations demonstrated key interactions between compound 7j and the active site of α-glucosidase, while molecular dynamics simulations confirmed the stability of the enzyme-ligand complex, reflected in low RMSD and RMSF values.

Type 2 diabetes mellitus (T2DM) remains a global health challenge, prompting the development of novel α-glucosidase inhibitors (AGIs) to regulate postprandial hyperglycemia. This study reports the design, synthesis, and evaluation of indole-based Schiff base derivatives (4a–j) bearing a fixed methoxy group at the C5 position. This substitution was strategically introduced to enhance lipophilicity, electronic delocalization, and π-stacking within the enzyme active site. Among the series, compound 4g (3-bromophenyl) exhibited the highest inhibitory activity (IC50 = 10.89 µM), outperforming the clinical reference acarbose (IC50 = 48.95 µM). The mechanism was supported by in silico analyses, such as the Density Functional Theory (DFT), molecular electrostatic potential (MEP) mapping, and molecular dynamics simulations, and CNN-based docking revealed that 4g engages in stable hydrogen bonding and π–π interactions with key residues (Asp327, Asp542, and Phe649), suggesting a potent and selective mode of inhibition. In silico ADMET predictions indicated favorable pharmacokinetic properties. Together, these results establish C5–methoxy substitution as a viable strategy to enhance α-glucosidase inhibition in indole-based scaffolds.

In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2- a ]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α -azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC 50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2- a ]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α -glucosidase (IC 50  = 16.4 ± 0.36 μM) and rat small intestine α -glucosidase (IC 50  = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

In this work, 1-phenyl-β-carboline-3-carboxamide-1,2,3-triazole- N -phenylacetamide skeleton as a novel scaffold was designed based on hybridization of moieties that were found in the potent α-glucosidase inhibitors. Fourteen derivatives 14a-n of this scaffold were synthesized by the efficient chemical reactions. In vitro anti-α-glucosidase assay demonstrated that all the new fourteen derivatives with IC 50 values ranging from 64.0 to 661.4 µM were more potent than positive control acarbose with IC 50 value of 750.0 and in vitro kinetic study revealed that the most potent compound among them, compound 14b , was an uncompetitive α-glucosidase inhibitor. Moreover, determination of the circular dichroism (CD) spectra demonstrated that compound 14b altered the secondary structure of α-glucosidase. Prediction of the pharmacokinetics and toxicity of the most potent compound 14b showed that our new compound had good toxicity profile as an oral drug candidate. Based on these findings, compound 14b can be considered as a promising candidate for the development of a new α-glucosidase inhibitor.

The increasing prevalence of type 2 diabetes has driven an increasing demand for safe and effective α-glucosidase inhibitors (AGIs). Given prior findings of α-glucosidase inhibitory activity in Paenibacillus spp., this study aims to evaluate the biosynthetic capacity and inhibitory potential of Paenibacillus sp. JNUCC 31. Genomic annotation of the strain JNUCC 31 revealed multiple biosynthetic gene clusters associated with secondary metabolite biosynthesis. Fatty acid profiling initially identified anteiso-C15:0 (57.32%) as the dominant fatty acid via GC-MS. Subsequently, the ethyl acetate extract from fermented cultures, which exhibited the highest α-glucosidase inhibitory activity (52.4 ± 0.7%), was purified and five known compounds were isolated: adenosine, uridine, 4-hydroxybenzaldehyde, dibutyl phthalate (DBP), and 1-acetyl-β-carboline. Among these, adenosine, uridine, and DBP have been previously reported as α-glucosidase inhibitors. Enzyme kinetics confirmed that uridine (K i = 153.35µM) functions as a competitive inhibitor, while adenosine (K i = 90.88µM) and DBP (K i = 516.22µM) act via a mixed-type inhibition mechanism. Molecular docking and molecular dynamics simulations demonstrated stable binding of these active compounds to human maltase-glucoamylase (MGAM, PDB ID: 2QMJ) and microbial isomaltase (PDB ID: 3A4A). Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis indicated favorable binding free energies (− 14.18 to − 36.5 kcal/mol), with key residues such as Trp406 (MGAM), Tyr158 and Gln279 (isomaltase) playing major roles in binding stabilization. Collectively, these findings highlight the strain JNUCC 31 as a promising microbial source of antidiabetic lead compounds.

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

In the present work, new quinolone-2-thio-acetamide-propane hydrazide-benzimidazole derivatives 12a-o were assigned as potent anti-diabetic agents that targeting α-glucosidase and α-amylase as two important targets in treatment of type 2 diabetes. General scaffold of these compounds was designed based on the reported potent α-glucosidase and α-amylase inhibitors and derivation was performed in acetamide moiety. In vitro evaluation of the new compounds 12a-o demonstrated that most of the synthesized compounds were more potent than standard inhibitor acarbose against α-glucosidase while all these new compounds were more potent than acaerbose against α-amylase. The most potent compound against both studied enzymes was compound 12n that was a 4-fluorophenylacetamide derivative. This compound was 5 and 23.8 folds more potent than acarbose against α-glucosidase and α-amylase, respectively, and with excellent binding energies in comparison to acarbose attached to active sites of these enzymes. Molecular dynamics and pharmacokinetic studies of compound 12n was also performed.

Wailupemycins H ( 1 ) and I ( 2 ) with a new skeleton coupled two 6-(2-phenylnaphthalene-1-yl)pyrane-2-one nuclei to a –CH 2 – linkage were identified from the culture of Streptomyces sp. OUCMDZ-3434 associated with the marine algae, Enteromorpha prolifera . Compounds 1 and 2 are two new α-glucosidase inhibitors with the K i /IC 50 values of 16.8/19.7 and 6.0/8.3 μM, respectively. In addition, the absolute configurations of wailupemycins D ( 3 ) and E ( 4 ) are also resolved in this paper for the first time.

A series of novel Schiff base derivatives (1–28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1 HNMR, 13 CNMR, and HR-ESI–MS spectroscopy. Except for compounds 22 , 26 , 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC 50  = 12.84 ± 0.52 µM), 4 (IC 50  = 13.64 ± 0.58 µM), 12 (IC 50  = 15.73 ± 0.71 µM), 13 (IC 50  = 16.62 ± 0.47 µM), 15 (IC 50  = 17.40 ± 0.74 µM), 3 (IC 50  = 18.45 ± 1.21 µM), 7 (IC 50  = 19.68 ± 0.82 µM), and 2 (IC 50  = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC 50  = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.