Potential Antidiabetic Agents Research Articles

Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies.

In this study, hydrazine clubbed thiazole derivatives (3a-3j) were obtained by Hantzsch thiazole synthesis and characterized by MS, 1H NMR, and 13C NMR. The inhibitory potentials of the derivatives against diabetes-related enzymes such as aldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) were experimentally determined, and the results were supported by molecular docking. The results showed that the derivatives (3a-3j) displayed varied degree of potential inhibitory activity, with KI values covering the following ranges: 5.47 ± 0.53 to 23.89 ± 1.46 nM for AR and 1.76 ± 0.01 to 24.81 ± 0.15 μM for α-GLY, and with IC50 values 4.94-28.17 μM for α-AMY, as compared to standard epalrestat and acarbose (KI: 34.53 ± 2.52 nM for AR and 23.53 ± 2.72 μM for α-GLY, respectively). The selective activity of these derivatives on antidiabetic enzymes may be important for the treatment of diabetes and may lead to the development of alternative new compounds for this purpose.

Design, Synthesis, and Biological Evaluation of Quinazolinone-Dihydropyrimidinone as a Potential Anti-diabetic Agent via GLUT4 Translocation Stimulation

Design, Synthesis, and Biological Evaluation of Quinazolinone-Dihydropyrimidinone as a Potential Anti-diabetic Agent via GLUT4 Translocation Stimulation

Design, Synthesis, and In Silico Molecular Docking Studies of Adamantanyl Hydrazinylthiazoles as Potential Antidiabetic Agents.

Diabetes mellitus (DM) is a widespread disease that poses a major threat to millions of people. To address this issue, we have synthesized seventeen new 4-(adamantan-1-yl)-(2-(arylidene)hydrazinyl)thiazoles (3a-q) via Hantzsch synthetic approach. The molecular structures of all the compounds were confirmed using FT-IR, 1H- and 13C-NMR spectroscopy, and HR-mass spectrometry. Protein kinase, α-amylase, glycation, and oxidation inhibition potential of all compounds were also investigated, and it was found that compounds 3b, 3c, 3e-3g, and 3i-3q have shown excellent α-amylase inhibition (IC50=7.91±0.07 to 28.57±0.1µM), compounds 3c, 3e, 3i, 3k, and 3p (IC50=30.6±0.06 to 37.8±0.005ppm) were found to be highly potent anti-glycating agents, and compounds 3c, 3g, 3h, 3k, and 3m were found to be more potent protein kinase inhibitors as compared to standards. The compounds 3b, 3c, 3d, 3e, 3f, 3g, 3i, 3k, 3l, 3m, 3n, 3p, and 3q have shown good antioxidant potential (IC50=27.5±0.09 to 48.8±0.09µM) as compared to standard ascorbic acid (IC50=51.3±0.1µM). The biocompatibility of all samples was also tested by employing brine shrimp lethality and in vitro hemolytic assays and was found to be safe to human erythrocytes at tested concentrations. Furthermore, the molecular docking simulation study also revealed that almost all synthesized compounds have potential interactions with target proteins at the molecular level.

Adenocarpine, Marmesin, and Lycocernuine from Ficus benjamina as Promising Inhibitors of Aldose Reductase in Diabetes: A Bioinformatics-Guided Approach.

Diabetes affects approximately 422 million people worldwide, leading to 1.5 million deaths annually and causing severe complications such as kidney failure, neuropathy, and cardiovascular disease. Aldose reductase (AR), a key enzyme in the polyol pathway, is an important therapeutic target for managing these complications. The high cost, severe side effects, and rising drug resistance in traditional diabetes treatments underscore the urgent need for novel AR-targeting antidiabetic agents. Ficus benjamina used in traditional medicine demonstrates promising potential for diabetes management. This study investigated the antidiabetic potential of F. benjamina phytocompounds targeting AR receptor employing a structure-based drug design approach to identify potential antidiabetic drug agents. Using molecular docking, ADMET analysis, molecular dynamics (MD) simulation, MM/GBSA, MM/PBSA, and DFT calculations, we identified three promising lead compounds: adenocarpine (- 9.2kcal/mol), marmesin (- 8.8kcal/mol), and lycocernuine (- 8.4kcal/mol). These compounds presented favorable pharmacokinetic, pharmacodynamic, and toxicity profiles, with a 500-ns MD simulation confirming their stability, supported by PCA and Gibbs FEL analysis. MM/GBSA study identified adenocarpine (- 72.53kcal/mol) as the best compound, outperforming marmesin (- 70kcal/mol) and lycocernuine (- 61.95kcal/mol). DFT analysis revealed that adenocarpine exhibited the highest molecular reactivity (3.914eV), while lycocernuine demonstrated the greatest kinetic stability (6.377eV). Marmesin and lycocernuine showed increased reactivity upon transitioning from the free states (4.441eV and 6.377eV, respectively) to the bound states (4.359eV and 6.231eV, respectively). These results could lead to the development of adenocarpine, marmesin, and lycocernuine as novel drug candidates for diabetes, warranting further in vitro and in vivo validation.

Isolation of a Unique Monoterpene Diperoxy Dimer From Ziziphora clinopodioides subsp. bungeana Together With Triterpenes With Antidiabetic Properties.

Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is used in traditional medicine for various purposes. Previous phytochemical studies focused on phenolic compounds, but triterpenoids were almost overlooked. The study focused on the isolation of compounds with dual antidiabetic activity from the aerial parts of Z. clinopodioides subsp. bungeana. Separation of CHCl3-soluble fraction by silica gel column chromatography using different mobile phases and purification of compounds by semi-preparative HPLC or preparative TLC. The structures of pure compounds were elucidated by 1D and 2D NMR experiments along with HRMS. Compound 1 was additionally identified by the single crystal X-ray diffraction method. α-Glucosidase inhibitory assay and GLUT4 expression and translocation in C2C12 myotubes were conducted to evaluate antidiabetic potential of isolated compounds. This phytochemical study led to the isolation of 20 compounds, including a unique monoterpene diperoxy dimer (1). Compounds 7 and 9-11 displayed more potent α-glucosidase inhibitory activity (IC50 45.3-135.3 μM) than acarbose used as a positive control (IC50 264.7 μM), while only pomolic acid (5) increased GLUT4 translocation in C2C12 myotubes in a significant manner. Extensive chromatographic separation led to the isolation and identification of a unique monoterpene diperoxy dimer (1) from aerial parts of Z. clinopodioides subsp. bungeana. Some triterpenes inhibited α-glucosidase, another increased GLUT4 translocation. Although none of the isolated compounds demonstrated dual antidiabetic activity, selected triterpenes proved to be potent antidiabetic agents in vitro.

A Computational Study of New Glitazones‐Sulphonylureas Hybrids as Potential Antidiabetic Agents

AbstractType 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with global cases expected to increase significantly in the coming decades. Existing treatments include sulphonylureas and thiazolidinediones (TZDs), which target insulin secretion and sensitivity. Hence, in this study, we have virtually designed a new hybrid of 2,4‐thiazolidinedione‐sulphonylureas 6a‐r by utilizing molecular hybridization of sulphonylurea and TZD moieties to enhance and improve their antidiabetic efficacy and bioavailability while eliminating their side effects. Furthermore, we have used computational techniques to evaluate the antidiabetic and pharmacokinetic properties of hybrids 6a‐r. The docking study of hybrids 6a‐r was assessed against five key proteins: α‐glucosidase, α‐amylase, PPAR‐γ, DPPIV, and SGLT2. The SwissADME and PkCSM results revealed the favorable pharmacokinetic profiles and acceptable toxicity. Amongst the 2,4‐thiazolidinedione‐sulphonylurea hybrids 6a‐r investigated, glitazone 6c and rhodanine 6k emerged as the best inhibitors of DPPIV and SGLT2 with binding free energies of −38.76 kcal/mol and −36.45 kcal/mol respectively, as well as corresponding docking scores of −8.78 and −6.28 kcal/mol. Furthermore, molecular dynamics simulations confirmed the stability of these binding to the enzymes' active sites. These findings suggest that glitazone and rhodanine hybrids can act as DPPIV and SGLT2 inhibitors, thus assisting in the drug discovery of new potential antidiabetic agents.

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 the biological study, compound 7f showed promising inhibitory activity against HPA with an IC50 value of 27.13 ± 1.02 μM and 7l exhibited better inhibition against HLAG with an IC50 value of 24.21 ± 1.12 μM. In addition, Lineweaver-Burk plot analysis suggested that 7l and 7f behaved as a mixed type of HLAG and HPA inhibitor and further, compound 7f showed significant PPAR-γ expression as compared to controls in a dose dependent manner; the expression can be attributed to its mapped pharmacophoric features with a phase screen score of 1.28 and vector score of 0.62. The proteins modulated by compounds include AMY2A, PPAR, and GAA proteins via MAPK, PPAR signalling pathways identified by cluster analysis and justified by molecular docking studies and MD trajectory analysis to evaluate the binding orientation and stability of the molecules, and the energy profiles of the molecules, both in complex with the protein, were assessed using MM/GBSA and DFT calculations, respectively. Finally, the pharmacokinetic profile was determined using ADMET analysis. Thus, from the above findings, it may demonstrate that rhodanine-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

New natural protein tyrosine phosphatase 1B inhibitors from Gynostemma pentaphyllum

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7∼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.

Novel alkoxy- and prenyl-xanthones derivatives as potential antidiabetic agents: Synthesis, in vitro evaluation and in silico studies

Novel alkoxy- and prenyl-xanthones derivatives as potential antidiabetic agents: Synthesis, in vitro evaluation and in silico studies

Jamun (Syzygium cumini Linn.) Seed Extract as a Potential Antidiabetic Agent: Effects on Blood Glucose Levels, Haematological Parameters and Biochemical Profiles in Alloxan-Induced Diabetic Albino Rats

Diabetes mellitus is rapidly increasing in India, making it essential to find alternative therapies that minimize side effects and improve patient outcomes. Safer treatment options are needed to manage the growing burden of this chronic condition effectively. This study evaluates the antidiabetic potential of Syzygium cumini seed extract (SCSEt) in alloxan-induced diabetic rats. Diabetes was induced by administering alloxan (120 mg/kg) in albino rats, and diabetes was confirmed with blood glucose levels ≥290 mg/dL. Rats were treated with SCSEt at doses of 2, 4, and 6 g/kg orally, with insulin (1.0 IU/kg/day) serving as a reference treatment. Over four weeks, SCSEt demonstrated a significant reduction in blood glucose levels compared to untreated diabetic controls, though less effective than insulin. Blood glucose levels in SCSEt-treated groups decreased from 286 ± 1.10 mg/dL (low-dose) to 110 ± 3.21 mg/dL (high-dose), compared to insulin-treated rats with levels of 112 ± 1.96 mg/dL. Haematological parameters improved with SCSEt, particularly at higher doses, where packed cell volume (PCV) reached 42.91 ± 0.98% and haemoglobin levels were 17.08 ± 2.06 g/dL. Biochemical analyses revealed reduced serum cholesterol and improved protein levels in high-dose SCSEt rats, with cholesterol dropping to 112 ± 1.92 mg/dL and protein rising to 6.39 ± 0.09 mg/dL. SCSEt also enhanced glucose tolerance, with high-dose SCSEt rats achieving the lowest glucose level of 104 ± 1.62 mg/dL at 100 minutes during the oral glucose tolerance test (OGTT). Although SCSEt was less effective than insulin in glucose management, its potential as a complementary therapy is supported by its significant improvements in glycemic control and lipid profile.

Exploring Thiazolidinedione-Naphthalene Analogues as Potential Antidiabetic Agents: Design, Synthesis, Molecular Docking and In-vitro Evaluation.

Thiazolidinedione-naphthalene analogues were synthesized and evaluated for antidiabetic activity as Pancreatic α-Amylase (PAA) and intestinal α-glucosidase (IAG) inhibitors. The activity of the compounds (14a-g,17a-k) is compared with acarbose as the standard drug and all the compounds shows good to moderate antidiabetic activity. In-vitro PAA and IAG inhibition assay is performed for the all compounds, the compounds 17e shows superior PAA and IAG inhibitory activity with respective to standard (IC50 = 12.455 ± 0.04 μM and 9.145 ± 0. 01 μM). The molecular interaction with PAA and IAG protein was also studied with the help of molecular docking studies using AutoDock software. while SwissADME and Osiris property explorer tools computed in-silico drug likeliness and toxicity properties. The in-silico results confirmed the 17e molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in-vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 14g and 17e has good antioxidant potential IC50 = 8.04 ± 0.02 μM and 6.36 ± 0.03 μM respectively among all compounds. In conclusion, in-vitro, in-silico antidiabetic and antioxidant studies revealed 17e compound was found to be potential compound.

Development of Potential Antidiabetic Agents using 2D and 3D QSAR, Molecular Docking and ADME Properties In-silico Studies of α-amylase Inhibitors

Development of Potential Antidiabetic Agents using 2D and 3D QSAR, Molecular Docking and ADME Properties In-silico Studies of α-amylase Inhibitors

Veratric Acid as a Potential Antidiabetic Agent: Molecular Docking and In vivo Enzyme Inhibition Studies with Insights from STz-NA Induced Diabetic Rat Model

Streptozotocin-nicotinamide (STz-NA) has proven to be an effective agent in inducing type 2 diabetes (T2DM) in experimental models due to its genotoxic impact on pancreatic β-cells. STz reduces nicotinamide adenine dinucleotide (NAD+) through the glucose transporter GLUT2, leading to cellular damage, DNA strand breaks, and cell death. Nicotinamide (NA), a biochemical precursor of NAD+ and poly-ADP-ribose-polymerase-1 (PARP-1) inhibitor, plays a crucial protective role by modulating NAD+ levels, which are essential in ATP production and other metabolic processes. Excessive DNA damage, however, triggers PARP-1 over-activation, depleting cellular reserves and resulting in cell necrosis. This study further investigates the antidiabetic and hepatoprotective effects of Veratric Acid (VA) by comparing it to Glibenclamide. Utilizing Computer-Aided Drug Design (CADD), VA was identified as a structurally similar compound with potential antidiabetic properties. Molecular docking studies targeting proteins, such as GLUT-1 (PDB ID: 4PYP) and 1BSI, along with in vivo assays in STz-NA-induced diabetic Wistar rats, were conducted. VA demonstrated significant binding affinity and molecular interactions comparable to standard antidiabetic agents, showing inhibitory effects on liver enzymes SGOT and SGPT, and supporting its potential role in diabetes management. Docking and histopathology results revealed that VA effectively reduced blood glucose, improved insulin levels, and enhanced liver function in diabetic rats. Additionally, VA promoted insulin secretion from pancreatic β-cells and upregulated insulin-related markers, with minimal hepatotoxicity compared to Glibenclamide. VA treatment significantly improved enzymatic and non-enzymatic antioxidant levels, lowered lipid peroxidation, and improved lipid profiles, which were confirmed by histopathological liver observations. Veratric Acid at low doses effectively modulates blood glucose and diabetes-related biochemical parameters, highlighting its promise as a safer, natural therapeutic alternative for diabetes treatment.

Novel Benzimidazole-Endowed Chalcones as α-Glucosidase and α-Amylase Inhibitors: An Insight into Structural and Computational Studies.

In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient 'one-pot' nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The 'one-pot' nitro reductive cyclization method offered a simple route for the preparation of benzimidazoles with excellent yield and higher purity compared to the other conventional acid- or base-catalyzed cyclization methods. 1H, 13C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound 7c, which was crystalized in the P1¯ space group of the triclinic crystal system. Hirshfeld surface analysis validates the presence of O-H..O, O-H…N, and C-H…O intermolecular hydrogen bonds. From the DFT calculations, the energy gap between the frontier molecular orbitals in 7c was found to be 3.791 eV. From the series, compound 7l emerged as a potent antidiabetic agent with IC50 = 22.45 ± 0.36 µg/mL and 20.47 ± 0.60 µg/mL against α-glucosidase and α-amylase enzymes, respectively. The in silico molecular docking studies revealed that compound 7l has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound 7l with α-glucosidase and α-amylase proteins.

Molecular modeling and synthesis of novel benzimidazole-derived thiazolidinone bearing chalcone derivatives: a promising approach to develop potential anti-diabetic agents.

Diabetes mellitus (DM) is a disorder which is raised at the alarming level and it is characterized by the hyperglycemia results from the impaired action of insulin, production of insulin or both of these simultaneously. Consequently, it causes problems or failure of different body organs such as kidneys, heart, eyes, nerve system. Since this disease cannot be completely cured until now, we aimed to design series of enzymes inhibitors and tested them for DM treatment. In this series, benzimidazole-based thiazolidinone bearing chalcone derivatives completed in a four step reaction and their structures were confirmed through various spectroscopic techniques. A significant efficacy on antidiabetic enzymes was observed, with IC50 values ranging from 25.05±0.04 to 56.08±0.07 μM for α-amylase and 22.07±0.02 to 53.06±0.07 μM for α-glucosidase. The obtained results were compared to those of the standard glimepiride drug (IC50=18.05±0.07 µM for α-amylase and IC50=15.02±0 .03 µM for α-glucosidase). The synthesized compounds showed promising antidiabetic potency. Moreover, a molecular docking study was conducted on the most active analogs of the compounds to better understand their interactions with the active sites of the targeted enzymes.

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones.

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a-d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.

Gas Chromatography-Mass Spectrometry and Fourier Transform Infrared Spectroscopy Analysis of Potential α-Glucosidase Inhibitors from Terminalia catappa Leaf Extracts

Aims: Postprandial hyperglyceamia is often caused by insulin insufficiency or cellular glucose uptake complications, and conventional treatments often yield undesirable side effects. The aim of the current work was to assess the α-glucosidase inhibitory activities of T. catappa leaf extracts and use spectroscopic techniques to partially characterize possible inhibitors. Study Design: Phytochemical screening, enzyme inhibition assay and spectrometric and spectroscopic characterization of bioactive compounds from leaf extract and fractions of T. catappa. Place and Duration of Study: The entire work was carried out at the Department of Applied Chemistry and Biochemistry, University for Development Studies, Ghana within nine months. Methodology: T. catappa leaf extract and fractions were qualitatively screened for phytochemicals and their biological activity assessed in α-glucosidase inhibition assay. The potential enzyme inhibitors were characterized by Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FT-IR) Spectroscopy. Results: Phytochemical screening of the extract and the various solvent fractions revealed the presence of alkaloids, flavonoids, saponins, flavanol glycosides, phenolics, and terpenoids. The α-glucosidase inhibition potential of the crude leaf extract was concentration-dependent with a half-maximal inhibitory concentration (IC50) of 337.5 µg/ml. Solvent fractions from the crude extract demonstrated α-glucosidase inhibitory activity with IC50 values ranging from 170.40 µg/ml for ethyl acetate (EtOAc) fraction to 71.90 µg/ml for n-hexane (n-Hex) fraction. Acarbose, the control drug, demonstrated significant α-glucosidase inhibition activity in a similar pattern with IC50 of 6.16 µg/ml. The enzyme inhibition kinetics parameters, specifically the Michaelis constant (KM) and Maximum reaction velocity (Vmax) values, suggested that the inhibition of α-glucosidase by T. catappa extract followed a competitive mode. GC-MS and FT-IR analysis of the n-Hexane fraction identified the compounds Eugenol, Urs-12-en-24-oic acid, 3-oxo-, methyl ester (+)-, phytol, trans-isoeugenol, α-amyrin, and squalene as the potential antidiabetic agents that might be responsible for reducing postprandial blood glucose levels. Conclusion: These findings show that T. catappa leaf extract contains α-glucosidase inhibitors and therefore serves as a valuable resource in the discovery of natural anti-diabetic agents.

Isatin-Fluorene Schiff base as potent antidiabetic agent: Synthesis, DFT calculations, Topology, in silico ADME analysis and molecular docking studies

Diabetes mellitus is a rapidly evolving planetary challenge with substantial societal, salubrity, and financial connotations. Derivatives of isatin with hydrazides, coumarin and aldehydes have proven to possess anti-diabetic activities. Hence, as a novel perspective, isatin was merged with a polycyclic aromatic compound, 2-amino fluorene to build a Schiff base compound with anti-diabetic activity. The anti-diabetic characteristics of the designed compound were scrutinised through in silico molecular docking studies. The designed compound, (Z)-3-((9H-fluoren-2-yl)imino)indolin-2-one (FII) was synthesised in the laboratory using a simple condensation procedure. NMR, HRMS, and Infrared spectral analyses did the experimental structural characterisation of FII. The theoretical investigations of FII were evaluated via density functional theory (DFT). The DFT studies provide insight into the structure, reactivity, and electronic properties of compound FII. The most stable conformation of FII was identified and confirmed by the B3LYP method. The basis set 6-31+G(d) was used for the calculations. The DFT studies include frontier molecular orbital (FMO) analysis to define the global parameters and molecular orbital energy gap, molecular electrostatic potential (MEP) map to find out the reactive sites and natural bond orbital (NBO) analysis for understanding the electron density and charge delocalisation of the title compound, FII. Topological analyses such as ELF, LOL, RDG, and QTAIM were performed to investigate the electronic bonding parameters. Additionally, UV-visible and photoluminescence spectra were performed to investigate the optical properties of FII. The biological potential of the title compound was validated by calculating the physicochemical properties using Lipinski's rule. The molecular docking of the synthesised compound, FII, has been computed using two different proteins, exhibiting inhibitory activity against the α-Glucosidase enzyme. The binding energy and ligand efficiency of both the selected proteins with the ligand molecule were also calculated.

Quinoline Based thiazolidinediones: Design, Synthesis, In Silico, In Vitro, Antioxidant and Antidiabetic Evaluation

AbstractIn the present research work a sequence of substituted quinoline based thiazolidinedione moieties (12a–h) were designed and synthesized as potential antidiabetic agents. Pancreatic α‐amylase (PAA) and intestinal α‐glucosidase (IAG) enzymes were considered as potential targets for effective treatment of diabetes. The potential of all compounds (12a–h) was assessed in vitro against PAA and IAG using acarbose as standard. The results suggested that compound 12h has shown superior PAA and IAG inhibitory activity with respective to standard (IC50 = 4.683 ± 0.06 µM and 2.456 ± 0.07 µM). Furthermore, using computational (in silico) studies like AutoDock and Desmond, predicted the significant binding interactions responsible for the activity of all compounds (12a–h) at the active site of enzymes, while SwissADME and Osiris property explorer tools computed in silico drug likeliness and toxicity properties. The RMSD, RMSF, Rg and protein ligand contacts, confirmed the stable binding of compound 12h and 12g with the both PAA and IAG proteins. The in silico results confirmed the 12h molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 12h has good antioxidant potential (IC50 = 5.04 ± 0.054 µM) among all other compounds. In conclusion, in vitro, in silico and antioxidant studies revealed 12h compound was found to be potential compound.

Structure-Activity Relationship of Hydrazinylthiazole-5-Carbaldehydes as Potential Anti-Diabetic Agents.

Diabetes is an emerging threat to the world due to large number of deaths reported within the last decade. To overcome its spread and complications, herein, we reported synthesis and anti-diabetic potential of twelve novel 2-[(arylidenyl)methylidene]hydrazinyl-1,3-thiazole-5-carbaldehydes (3 a-l). All compounds have shown good to excellent α-amylase inhibitory activity, among them ortho substituted analogues, the compound 3 a (IC50=14.6 mM) and 3 l (IC50=17.9 mM) showed excellent inhibition potential due to the strong electron donating nature of the substituents attached at the aryl ring. The compounds 3 a-3 h (IC50=6.70-10.80 ppm) exhibited excellent anti-glycation potential as compared to standard amino-guanidine (IC50=11.92 ppm). Almost all the tested compounds are found biocompatible and very safe to the human erythrocyte cells at all tested concentrations. The molecular docking results have found that the binding energy score of all the tested compounds against human serum albumin protein (pdb: 1AO6) is between -5.1827 and -6.8661 kcal/mol which is far better than standard amino-guanidine (-4.234 kcal/mol).