Potential Antidiabetic Agents Research Articles

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1β (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at −7.489, −6.381, −6.742, −7.202, and −8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent. Communicated by Ramaswamy H. Sarma

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that targetdrug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and-CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

THERAPEUTIC EFFECT OF MORINGA LEAF DECOCTION TO DECREASE BLOOD SUGAR LEVELS AND HBA1C VALUES OF DIABETICS TYPE II DIABETES MELLITUS AT KARANG PANJANG AMBON HEALTH CENTER

Abstract Type 2 Diabetes (T2DM) is the most common type of diabetes and is still become one of the causes of death. One way of managing T2DM is mostly by controlling blood sugar, HbA1c levels, developing a healthy diet and herbal alternative therapies. One intervention that does not require expensive costs can be done to improve treatment outcomes in patients with T2DM by controlling blood glucose levels and HbA1c is through moringa leaf decoction therapy. Moringa oleifera (Moringa oleifera) contains and benefits from moringa leaves which have high nutritional value, are rich in minerals, vitamins, and other important phytochemicals. Extracts from the leaves are used to treat malnutrition, as a potential antioxidant, anticancer, anti-inflammatory, antidiabetic and antimicrobial agents. This study aims to analyze the therapeutic effect of moringa leaf decoction to decrease blood sugar and HbA1C levels of Type II diabetes mellitus patients in Karang Panjang Ambon Health Center. Sampling technique using consecutive sampling in one intervention group. The study was conducted for seven days with the number of subjects involved in this study as many as 27 people who were measured blood sugar levels and HbA1C before and after treatment. This study is a type of quantitative research using pre-experimental approach one group pre-post design. The results of the study obtained the value of SIG 0.000 < 0.050 this states that there is a significant effect of moringa leaf decoction therapy to reduce blood sugar levels and HbA1c values in patients DM Type II Keywords: moringa leaves, diabetes mellitus Type II, blood sugar, HbA1c

QSAR of Oxazinanone Derivatives As 11-Β Hydroxysteroid Dehydrogenase Type 1 Inhibitor A Potent Anti Diabetic Agent

11-β hydroxysteroid dehydrogenase type 1 is a key enzyme accountable for the interconversion of physiologically inert cortisone to active cortisol thus presents an effective target for the development of pharmacologically active anti diabetic agents focused on manage blood glucose levels, improve insulin sensitivity. The 11β-HSD1 facilitates intracellular cortisol construction that have a disease-causing role in type 2 diabetes and the co-morbidities that it causes. Drugs in habiting the enzyme 11 β-HSD1 offers a potential therapy to lessen the type 2 diabetes. Oxazinanone ring has shown activities as antitumor, antihypertensive, antibacterial, anti-inflammatory, antioxidant and many more. Oxazinanone ring have emerged as potent inhibitors of 11β-HSD1 enzyme. QSAR of Oxazinanone derivatives is performed with a goal of elucidating the key characteristics that cause their anti-diabetic action. QSAR is the most widespread method to ligand-based drug design. It is supposed that structures of the molecules are directly proportional with biological activities, and thus, the biological activities can be altered with any structural changes. The process involves computational or mathematical models to find important correlations between a series of structures and functions. Step wise partial least square, multiple linear regressions, and feed forward neural network were used in a QSAR investigation on enzyme (IC50 nM). The developed models were cross confirmed by the ‘‘leave one out’’ method. The model reveals the significance of steric parameter Verloop B1 (Substitution 1) and Total lipole molecular descriptor.Total lipole bear a resemblance to lipophilicity which is a ratio of the capability of molecules to transfer between oily partition and aqueous partition. These descriptors will have an impact on the design and expansion of novel anti-diabetic 11-hydroxysteroid dehydrogenase type 1 inhibitors.

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.

Uptake of vanadium and its intracellular metabolism by Coprinellus truncorum mycelial biomass

BackgroundFungi absorb and solubilize a broad spectrum of heavy metals such as vanadium (V), which makes them a main route of its entry into the biosphere. V as vanadate (V5+) is a potential medical agent due to its many metabolic actions such as interaction with phosphates in the cell, and especially its insulin-mimetic activity. Antidiabetic activity of V-enriched fungi has been studied in recent years, but the biological and chemical bases of vanadium action and status in fungi in general are poorly understood, with almost no information on edible fungi. MethodsThis manuscript gives a deeper insight into the interaction of V5+ with Coprinellus truncorum, an edible autochthonous species widely distributed in Europe and North America. Vanadium uptake and accumulation as V5+ was studied by 51V NMR, while the reducing abilities of the mycelium were determined by EPR. 31P NMR was used to determine its effects on the metabolism of phosphate compounds, with particular focus on phosphate sugars identified using HPLC. ResultsVanadate enters the mycelium in monomeric form and shows no immediate detrimental effects on intracellular pH or polyphosphate (PPc) levels, even when applied at physiologically high concentrations (20 mM Na3VO4). Once absorbed, it is partially reduced to less toxic vanadyl (V4+) with notable unreduced portion, which leads to a large increase in phosphorylated sugar levels, especially glucose-1-phosphate (G1P) and fructose-6-phosphate (F6P). ConclusionsPreservation of pH and especially PPc reflects maintenance of the energy status of the mycelium, i.e., its tolerance to high V5+ concentrations. Rise in G1P and F6P levels implies that the main targets of V5+ are most likely phosphoglucomutase and phosphoglucokinase(s), enzymes involved in early stages of G6P transformation in glycolysis and glycogen metabolism. This study recommends C. truncorum for further investigation as a potential antidiabetic agent.

Polyphenol-Standardized Aphanamixis polystachya Leaf Extract Ameliorates Diabetes, Oxidative Stress, Inflammation, and Fibrosis in Streptozotocin-Induced Diabetic Rats

Background. Diabetes is a rising disorder that affects millions of people annually. It also creates more complications, such as neuropathy, oxidative stress, and hepatic and kidney impairment. Aphanamixis polystachya plant, which possesses multiple medicinal values, is used in this study to explore its potential in treating diabetes. Methods. A single dose (65 mg/kg) of intraperitoneal streptozotocin injection was utilized to mediate diabetes in Sprague-Dawley rats. Diabetic animals were treated orally with 250 or 500 mg/kg of standardized leaves’ extract of A. polystachya (AP) for 28 days to evaluate the antidiabetic and organ-protective effects of the plant. Different biochemical and histological markers are measured according to the established protocol. Results. Our results demonstrated a significant decrease in blood glucose (p <0.001) and HbA1c (p <0.05) levels in the diabetic animal after administering AP (250 and 500 mg/kg doses) compared to the control groups. AP can also regularize lipids, glycogen, alanine aminotransferase, and aspartate aminotransferase. Furthermore, serum urea nitrogen and creatinine decreased after treatment with AP in diabetic rats. AP also reduced oxidative stress markers and showed a substantial elevation in antioxidant enzymes in diabetic animals. Overall, AP at 500 mg/kg revealed comparable results against the standard antidiabetic drug glyburide. Besides, the histological investigation showed the AP’s efficacy in attenuating kidney tissue inflammation and damage. HPLC data elucidated that the AP leaf extract contains polyphenols with potential antioxidant, antidiabetic, and organ protective agents: gallic acid, rutin hydrate, and quercetin hydrate. Conclusion. Taken together, AP may be one of the potential sources of antidiabetic agents.

Synthesis and biological evaluation of β-lactams as potent antidiabetic agents

The in vitro, in vivo, antioxidant, molecular docking, and physiochemical studies supported the potential development of β-lactam B9 as an orally active antidiabetic drug due to its significant α-glucosidase inhibitory activity.

Global research trend related to antidiabetic agent on Nigella sativa: A bibliometric analysis based on Scopus from 1987-2023

Several research studies have demonstrated the efficacy of Nigella sativa in enhancing the clinical condition associated with diabetes. However, there has been a lack of extensive use of bibliometric methods in this particular area of study. In response to this gap, we conducted a bibliometric analysis with a focus on exploring research related to N. sativa as a potential antidiabetic agent. We gathered bibliographic data from pertinent studies in the Scopus database, comprising 105 papers published between 1987 and 2023. We conducted the bibliometric analysis using Visualization of Similarities Viewer (VOSviewer) version 1.6.20. Our investigation revealed Alexandria University in Egypt as the most prolific institution, and the journal Evidence-Based Complementary and Alternative Medicine emerged as the primary publication platform for research on the antidiabetic agent of N. sativa. Egypt demonstrated notable prominence as the foremost country in both productivity and collaboration within this field. From 1987 to 2023, most studies focused on the effects of N. sativa on diabetes and how it is used to treat it. Other major issues included its immune-boosting, cardiovascular-healthy, and cancer-fighting capabilities.

Novel rhodanine-thiazole hybrids as potential antidiabetic agents: A structure-based drug design approach

New rhodanine-thiazole clubbed compounds (7a-7l) were synthesised and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro HPA, HLAG inhibition, and Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) expression assays. Through...

Synthesis, molecular docking study, MD simulation, ADMET, and drug likeness of new thiazolo[3,2-a]pyridine-6,8-dicarbonitrile derivatives as potential anti-diabetic agents.

There are numerous uses for the pharmacological effects of thiazolo-pyridine and its derivatives. The main objective of the study was to synthesis 10 novel derivatives of thiazolo[3,2-a] pyridine-6,8-dicarbonitrile with a 22-78% yield, with a focus on their potential anti-diabetic properties. We investigated the interactions between these compounds and the enzyme α-amylase through an in silico study involving molecular docking. According to the docking analysis results, the resulting compounds had advantageous inhibitory properties. With a docking score of -7.43 kcal/mol against the target protein, compound 4e performed best. The stability root-mean-square deviation (RMSD) showed that the complex stabilizes after 25 ns and with minor perturbation at 80. The RMSF values of the ligand-protein complex indicate that the following residues have interacted with compound 4e during the MD simulation: Trp58, Trp59, Tyr62, Gln63, His101, Val107, lle148, Asn152, Leu162, Thr163, Gly164, Leu165, Asp197, Ala198, Asp 236, Leu237, His299, Asp300, and His305. Moreover, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one suggest that they have the potential to be effective inhibitors of α-amylase and should be considered for further research. Nevertheless, it is crucial to ascertain the in vivo and in vitro effectiveness of these compounds through biochemical and structural investigations.

Synthesis, in vitro enzyme kinetics and molecular docking studies of the 2-formylphenyl sulfonates and their hydrazone derivatives as potential anti-diabetic and anti-inflammatory agents

The in vitro anti-diabetes and anti-inflammatory inhibitory activities of the synthesized 2-formylphenyl sulfonates and their hydrazone derivatives were evaluated through enzymatic assays as potential α-glucosidase and lipoxygenase (LOX-15) inhibitors. The preliminary inhibitory results obtained, revealed that the prepared compounds are good inhibitors of α-glucosidase as compared to lipoxygenase (LOX-15). Compounds 2 g and 3 h were found to exhibit significant inhibitory activities against α-glucosidase with IC50 values of 3.1 µM and 2.6 µM, respectively. Moderate inhibitory activity was also observed for compound 3a (IC50 = 7.3 µM) against this enzyme. Enzyme kinetics studies of the most active compound (3 h) suggested a mixed mode of inhibition for this compound against α-glucosidase. The molecular docking and molecular dynamics simulation of compounds 2 g, 3a and 3 h into the active sites of α-glucosidase were used to predict the binding modes and structure activity relationship for these compounds. The molecular dynamics simulation demonstrated that compound 3 h significant inhibitory activity is due to its ability to bind to both the catalytic and secondary sites of the enzyme.

Identification of Potential Plant-Derived Pancreatic Beta-Cell-Directed Agents Using New Custom-Designed Screening Method: Gymnema sylvestre as an Example.

Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore β-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on β-cells islets of Langerhans. Currently, there are no defined criteria for screening of β-cell-directed plant-based remedies as potential antidiabetic agents. In this review, we have identified certain criteria/characteristics that can be used to generate a "screening portfolio" to identify plant extracts as potential β-cell-directed agents for the treatment of T2DM. To validate our screening method, we studied the potential therapeutic efficacy of a Gymnema sylvestre (GS) extract using the screening criteria detailed in the review. Six criteria have been identified and validated using OSA®, a GS extract. By using this screening method, we show that OSA® fulfilled most of the criteria identified for an effective β-cell-directed antidiabetic therapy, being an effective insulin-releasing agent at nontoxic concentrations; maintaining β-cell insulin content by stimulating a concomitant increase in insulin gene transcription; maintaining β-cell mass by protecting against apoptosis; and being effective at maintaining normoglycemia in vivo in a mouse model and a human cohort with T2DM. The present review has highlighted the importance of having a screening portfolio for plant extracts that have potential antidiabetic effects in the treatment of T2DM. We propose that this screening method should be adopted for future studies to identify new β-cell-directed antidiabetic plant derived agents.

A Flavonoid-rich Fraction of Alternanthera pungens Ameliorates Hyperglycaemia -mediated Memory Dysfunction in Diabetic Rats

The central nervous system (CNS) undergoes alterations due to persistent hyperglycemia and cholinergic dysfunction, leading to cognitive impairment associated with diabetes (T2DM). Animal studies have shown that acetylcholinesterase (AChE) inhibitors and anti-diabetics are effective. Considering the impressive potential of natural products in treating DM and AD, the present research set out to assess the neuroprotective effects of a methanolic extract of Alternanthera pungens (MEAP) against cognitive impairment in mice caused by hyperglycemia. Hence, we used the mobile workforce management (MWM) and enterprise performance management (EPM) assays to analyze for cognitive impairment in diabetic rats. 30 days after the initiation of T2DM, rats had hyperlipidemia, increased escape latency in EPM tasks, and decreased time spent in the TSTQ during probe trials in the MWM. They also displayed notable and persistent hyperglycemia throughout training trials. Changes in blood glucose, lipid, and liver profiles, as well as performance in MWM and EPM tests, were averted in STZ-induced T2DM rats treated with MEAP (200 and 400 mg/kg). In a separate series of experiments, flavonoids (i.e., quercetin and rutin) were detected by the standardization of the extract using high performance thin layer chromatography (HPTLC). Inhibitory actions against alpha-amylase and alpha-glucosidase demonstrate that both of these flavonoids are potent antidiabetic agents that reduce intestinal glucose absorption. Lastly, the inclusion of these flavonoids in the extract from A. pungens is responsible for its action, suggesting that it may provide a novel strategy for preventing cognitive deterioration in diabetes.

Bioassay-guided discovery and identification of new potent α-glucosidase inhibitors from Morus alba L. and the interaction mechanism

Ethnopharmacological relevanceMorus alba L. (mulberry) is a well-known medicinal species that has been used by herbalist doctors for the treatment of diabetes for a long history, and modern ethnopharmacological studies have demonstrated the ameliorating effects of different mulberry extracts toward diabetes-related symptoms and identified a number of α-glucosidase inhibitors as hypoglycemic ingredients. Aim of the studyThe present study aims to explore new potent α-glucosidase inhibitors from the root bark of M. alba (known as Sang-Bai-Pi in traditional medicine) based on an in vivo antidiabetic evaluation of its extract fractions and further characterize the preliminary mechanism of the new active constituents. Materials and methodsα-Glucosidase inhibitory assay and diabetic mice model were used to locate and evaluate the active fractions from the extract. Diverse separation techniques (e.g. Sephadex LH-20 column chromatograph (CC) and HPLC) and spectroscopic methods (e.g. MS, NMR and ECD) were employed to isolate and structurally characterize the obtained constituents, respectively. Fluorescence quenching, kinetics and molecular docking experiments were conducted to investigate the enzyme inhibitory mechanism of the active compounds. ResultsThe 80% ethanol eluate from the macroporous resin CC exerted good antidiabetic effects in the tested mice. Fifty-two flavonoids including 22 new ones were then separated and identified, and most of them showed strong inhibition against α-glucosidase with their structure-activity relationship being also discussed. The four new most active ingredients were further characterized to be mixed type of α-glucosidase inhibitors, and their binding modes with the enzyme were also explored. ConclusionsOur current work has demonstrated that the root bark of M. alba is an extremely rich source of flavonoids as potent α-glucosidase inhibitors and potential antidiabetic agents, which makes it a promising candidate species to develop new natural remedies for the prevention and treatment of diabetes.

Prospects for the Search for New Antidiabetic Agents Among Vanadium-containing Complex Compounds (Review)

Introduction. The epidemic increase in the incidence of diabetes mellitus (DM) makes it urgent to search for new antidiabetic agents. In clinical practice, there is an urgent question about improving and/or replacing insulin therapy for the disease. Vanadium compounds are of particular interest in connection with the identification of their multifactorial effects on the body, including insulin-like and hypoglycemic properties, which opens up prospects for the creation of a new generation of therapeutic agents for the treatment of types 1 and 2 diabetes. The focus of this review is on the structure and antidiabetic properties of vanadium complexes.Text. This review is devoted to the analysis of scientific literature on studies of vanadium-containing compounds as potential antidiabetic agents. The mechanisms of antidiabetic activity of vanadium-containing complex compounds are discussed. The prospects for searching for oxovanadium(IV) complexes with O4-coordination have been assessed.Conclusion. As a result of the analysis of the literature data, it was found that vanadium-containing complex compounds have a significant potential for use as antidiabetic agents. The relevance of the search for highly effective oxo-vanadium metal complexes based on ligands close to endogenous substrates, for example, based on derivatives of aroylpyruvic acid, is shown.

Design, Synthesis, and Molecular Docking Studies of Integrated Benzylidenethiazolidine‐2,4‐Dione and Thieno[2,3‐d]pyrimidine‐6‐Carboxylate Derivatives as Potent Antidiabetic agents

AbstractThe present work describes the synthesis of new series of 5‐arylidene‐thiazolidine‐2,4‐dione, thieno[2,3‐d]pyrimidine‐6‐carboxylate derivatives 9 a–o. A variety of spectroscopic techniques like IR, 13CNMR, 1HNMR and LCMS were used to establish the presence of the every synthesized scaffold. The antioxidant activity of the target compounds has been studied by three different methods indicated the significant DPPH, NO and H2O2. Further, all the derivatives were evaluated for the in vitro antidiabetic potential against human pancreatic α‐amylase (PDB ID: 5NN3) and human lysosomal acid α‐glucosidase (PDB ID: 2QV4) enzymes followed by Molecular docking studies to ascertain the binding interactions of the compounds with the enzymes. The compounds 9 b and 9 g containing methoxy groups were found to exhibit potent antidiabetic and antioxidant activity. Therefore, it was rationalized that two privileged pharmacophores i. e. aryledenethiazolidine‐2,4‐dione and thieno[2,3‐d]pyrimidine‐6‐carboxylate assimilated hybrids, may be beneficial as lead template for the advance of future anti‐diabetic agents. Thus, benzylidenethiazolidine‐2,4‐dione and thieno[2,3‐d], the two preferred pharmacophores, were rationalized. Assimilation of ‐pyrimidine‐6‐carboxylate hybrids could be advantageous as a lead template for the development of new anti‐diabetic drugs.

Structural Characterization, Antioxidant, Antidiabetic and Antimicrobial Activities of Citrus Limettarisso, Citrus Nobilis X Citrus Deliciosa and Citrus Maxima

Background: The pharmacological properties of citrus fruits have long been recognized in traditional medicine, with recent scientific studies corroborating their potential as sources of natural bioactive compounds. Citrus limettarisso, Citrus nobilis x Citrus deliciosa, and Citrus maxima, in particular, have garnered attention for their antioxidant, antidiabetic, and antimicrobial properties. Prior research has highlighted these species' capabilities, with various studies reporting on their significant health benefits. Objective: This study aims to evaluate and compare the antioxidant, antidiabetic, and antimicrobial activities of essential oils extracted from the peels of Citrus limettarisso, Citrus nobilis x Citrus deliciosa, and Citrus maxima, thereby contributing to the understanding of their potential therapeutic applications. Methods: Essential oils were extracted from the peels of the three citrus species using hydro distillation. The antioxidant activity was assessed through Total Phenolic Content (TPC), Total Flavonoid Content (TFC), and DPPH Radical Scavenging Assay. Antiglycation potential and alpha-amylase inhibition were evaluated for antidiabetic properties, while antimicrobial activity was determined using the Agar Well Diffusion Method. Results: Citrus limettarisso showed the highest TPC (301.4474 ± 2.930402 mg GAE/100g) and significant antioxidant activity (68.26347% DPPH scavenging). Citrus maxima exhibited a high TFC (143.8727 ± 5.454545 mg CE/100g) but lower TPC (115.8333 ± 3.553444 mg GAE/100g). Citrus nobilis x Citrus deliciosa demonstrated considerable TPC (244.1667 ± 5.862774 mg GAE/100g) and TFC (50.17576 ± 0.457566 mg CE/100g). Antiglycation and alpha-amylase inhibition assays revealed Citrus limettarisso as the most potent antidiabetic agent with the highest inhibition percentages. All three species showed significant antimicrobial activity. Conclusion: The study confirms the substantial pharmacological potential of Citrus limettarisso, Citrus nobilis x Citrus deliciosa, and Citrus maxima, particularly in terms of their antioxidant and antidiabetic properties. Citrus limettarisso emerged as the most potent in most assays, underscoring its potential for therapeutic use. These findings support the use of these citrus species as natural sources of bioactive compounds for health and medical applications. It carries special importance for public health advancements.

Appraisal of the anti-diabetic potential of polyphenolic compounds from Viscum combreticola Engl.: In vitro α-glucosidase inhibition, LC-ESI-QTOF-MS coupled to pre-column DPPH antioxidative assay, network pharmacology and molecular docking analysis

Viscum combreticola Engl. is currently used in African medicine for treating various ailments including diabetes. However, modernizing plant-based traditional medicine is a considerable challenge due to lack of scientific information linked to its therapeutic efficacy given the complexity of plant extracts. Herein, methanolic extracts were evaluated for their anti-diabetic and antioxidative properties through the α-glucosidase in vitro inhibition assay and LC-ESI-Q-TOF-MS coupled to pre-column DPPH assay, respectively. Furthermore, metabolic profiling of V. combreticola extracts was conducted using UHPLC-q-TOF-MS technique. The identified chemically diverse polyphenols comprising of 19 diacylated chlorogenic acids (CGAs) and 12 flavonoids were explored for their mode of action in managing type 2 diabetes mellitus (T2DM) using network pharmacology. Systematic pharmacological analysis revealed that CGAs and flavonoids characterized by structural similarities or analogous spatial arrangements exhibited interactions with identical target proteins. Isomers of CGAs diacylated at carbon positions 3,4 (3,4-diCQA; 3-p-Co-4-CQA and 3-C-4-p-CoQA) as well as 4,5 (4,5-diCQA;4-C-5-p-CoQA; and 4-p-Co-5-CQA) of quinic acid were found to be hub therapeutic agents against T2DM related target proteins. The investigated CGAs and flavonoids could be playing a major role in the management of T2DM and its complications by synergistically regulating key protein targets. These include matrix metalloproteinase 2 (MMP2), caspase 3 (CASP3), protein kinase C alpha and delta (PRKCA and PRKCD), which are related to T2DM hub pathways such as the lipid and atherosceloresis, AGE-RAGE signalling pathway for diabetes complications and diabetic cardiomyopathy signalling pathways. Finally, molecular docking studies revealed that viscutin 2 and 3,4-diCQA were key potential inhibitors of α-glucosidase and MMP2, respectively. Therefore, the findings of this study suggest that isomerism in compounds might have pharmacological implications. Lastly, the anti-T2DM therapeutic effects of the polyphenols investigated in this study can serve as potential anti-diabetic agents for future experimental validation, particularly paying attention to isomerism.