Standard Acarbose Research Articles

HPLC-DAD Phenolic Composition, Antioxidant, Anticholinesterase, Antidiabetic and Anti-quorum Sensing Properties of Bitter Kola (Garcinia kola) and Kolanut (Cola acuminata)

Pharmacognosy Research,2023,15,2,373-383.DOI:10.5530/pres.15.2.040Published:February 2023Type:Original Article Authors:Sameh Boudiba, Selcuk Kucukaydin, Alfred Ngenge Tamfu, Kom Blaise, Aristide Mfifen Munvera, Yasmine Arab, Ozgur Ceylan, and Rodica Mihaela Dinica Author(s) affiliations:Sameh Boudiba1, Selcuk Kucukaydin2, Alfred Ngenge Tamfu3,4,*, Kom Blaise5, Aristide Mfifen Munvera6, Yasmine Arab7, Ozgur Ceylan4, Rodica Mihaela Dinica8 1Department of Matter Sciences, Faculty of Exact Sciences, Natural and Life Sciences, Larbi Tebessi University, Tebessa, ALGERIA. 2Department of Medical Services and Techniques, Koycegiz Vocational School of Health Services, Mugla Sitki Kocman University, Mugla, TURKEY. 3Department of Chemical Engineering, School of Chemical Engineering and Mineral Industries, University of Ngaoundere, Ngaoundere, CAMEROON. 4Food Quality Control and Analysis Program, Ula Ali Kocman Vocational School, Mugla Sitki Kocman University, Mugla, TURKEY. 5Department of Chemistry, Faculty of Science, University of Ngaoundere, Ngaoundere, CAMEROON. 6Department of Organic Chemistry, Faculty of Science, The University of Yaounde I, Yaounde, CAMEROON. 7Laboratory of Biomolecules and Plant Breeding, Life Science and Nature Department, Faculty of Exact Science and Life Science and Nature, University of Larbi Ben Mhidi Oum El Bouaghi, ALGERIA. 8Dunarea de Jos University, Faculty of Sciences and Environment, Department of Chemistry, Physics and Environment, Galati, ROMANIA. Abstract:Background: Eating Cola acuminata and Garcinia cola nuts in African societies symbolizes in socio-cultural hospitality. They stimulate the nervous system, reduce fatigue and sleep. Objectives: To determine the phenolic composition and bioactivities of G. kola and C. acuminata. Materials and Methods: Hydro-ethanol extracts of the nuts were prepared and their phenolic profiles determined using HPLC-DAD. Antioxidant, anticholinesterase, antidiabetic, antimicrobial, antibiofilm and anti-quorum sensing properties were determined. Results: The most abundant phenolic compound was caffeic acid (105.4±0.75 mg/g) in C. acuminata and myricetin (277.2±0.90 mg/g) in G. kola. The extracts showed good antioxidant activity in five complementary assays and G. kola was more active than both α-tocopherol and BHA standards in the DPPH•, CUPRAC and ABTS•+ assays while C. acuminata was more active than only the α-tocopherol standard in the same assays. Activities were close to those of standards in the β-Carotene-linoleic acid and metal chelation assays. Both extracts had good inhibition of Butyrylcholinesterase (BChE) and Acetylcholinesterase (AChE) with IC50 values 63.27±0.98 μg/mL and 94.15±1.05 μg/mL for C. acuminata and G. kola respectively compared to 5.50±0.25 μg/mL for galantamine in the AChE assay. In the BChE assay, the inhibitory activity was higher for G. kola (IC50 = 38.66±0.80 μg/ mL) that the standard galantamine (IC50 = 42.20±0.48 μg/mL) while that for C. acuminata (IC50 = 87.31±0.77 μg/mL) was moderate. The extracts inhibited α-amylase and α-glucosidase with G. kola (IC50=18.43±0.74 μg/mL) being more active than standard acarbose (IC50=20.52±0.84 μg/mL in the α-glucosidase assay. The nuts could inhibit expression of virulence factors in Chomobacterium violaceum CV12472 by disrupting violacein production and flagellated Pseudomonas aeruginosa PA01 by disrupting swarming motility. Conclusion: The results indicate good nutraceutical potential of both nuts. Keywords:Anticholinesterase, Antidiabetic, Antioxidant, Cola acuminata, Garcinia kola, Quorum-sensing inhibition.View:PDF (380.01 KB)

Development of coumarin tagged 1,2,3-triazole derivatives targeting α-glucosidase inhibition: Synthetic modification, biological evaluation, kinetic and in silico studies

Coumarin derivatives have been demonstrated as promising anti-diabetic compounds through α-glucosidase inhibition. This is a ubiquitous brush border membrane-bound enzyme and an effective curative target for the treatment of diabetes. A novel series of compounds namely N-aryl-2-(4-(((2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetamide 8a-p were synthesized conveniently. Furthermore, the α-glucosidase inhibition potential of synthesized compounds was investigated, and based on the obtained data, all derivatives showed excellent inhibitory effect against α-glucosidase compared to standard antidiabetic drug acarbose. Among them, compounds 8d and 8j were represented to be the most potent ones with IC50s = 6.4 ± 0.1 and 3.5 ± 0.1, respectively. Kinetic enzymatic assays investigated that compound 8j was a competitive inhibitor of the enzyme, and further studies represented a Ki value of 2.2 µM for compound 8j. Moreover, the binding energy for compound 8j was obtained -8.30 kcal/mol in the molecular docking study. The structural dynamics incurred by the most potent compound have been investigated through the RMSD and RMSF studies. Underlining their physicochemical parameters, they have promising drug-like properties.

Anti‐Diabetic Activity of Flavonol Glucosides From Fumana montana Pomel: In vitro Analysis, In Silico Docking, ADMET Prediction, and Molecular Dynamics Simulations

AbstractOne of the major challenges in type 2 diabetes is the inhibition of the enzyme alpha‐amylase, since many molecules targeting this enzyme based on or derived from medicinal plants have been synthesized to counteract the α‐amylase action. The present study investigated the in‐vitro and in‐silico antidiabetic capacities of three flavonol glucosides obtained from the plant Fumana montana Pomel using α‐amylase inhibition model. α‐amylase binding interaction with the studied compounds was examined using ultraviolet‐visible absorption spectroscopy technique. Molecular docking and ADMET prediction were also performed for the three phytoconstituents towards human pancreatic alpha‐amylase receptor. The in vitro results revealed that both compound FG1 and FG3 showed a higher antidiabetic activity (84.00±0.12 and 85.36±0.12 μg/ml respectively) than that of standard antidiabetic acarbose (91.12±0.11). The value of the binding free energy ranging from −31.66±0.07 to −32.68±0.03 KJ mol−1 demonstrated the spontaneity and the strong binding betweenα‐amylase and the studied phytoconstituents. Molecular docking study indicated the preferred binding site and binding mode, and further suggested that the binding mode of the three compounds to the target enzyme is of hydrogen bonding and hydrophobic forces. Further analysis by molecular dynamic simulation studies showed that FG2 was stable in the HPA active site. In vitro and in‐silico results showed that the studied phytoconstituents interacted with α‐amylase and their binding interaction resulted in reduction of the enzyme's activity.

Some of the organic ligand transition metal complexes can serve as potent α-glucosidase inhibitors: in-vitro, kinetics and in-silico studies

Inhibition potential of synthesized bi-ligand metal complexes of 4-aminoantipyrine Schiff bases (3–14) and mixed-ligand metal complexes of cysteine-moxifloxacin (15–24) were analyzed for their inhibition potential against α-glucosidase and the type of inhibition was assessed by their kinetics and molecular docking studies. The Hg metal complex of cysteine-moxifloxacin (17) showed promising inhibition. Furthermore, the Ag (14), Hg (6) and Cu (4) metal complexes of Schiff base ligand of 4-aminoantipyrine also presented high activity potential. The IC 50 values of these compounds are 2.36 ± 0.14 μM, 48.8 ± 2.20 μM, 189 ± 17.00 μM and 264 ± 10.00 μM, respectively, as compared to standard drug acarbose with IC50 value of 378.2 ± 0.12 μM. Kinetic studies of compounds (17 and 14) from both series of metal complexes indicated that they are noncompetitive inhibitors of α-glucosidase. Molecular docking studies showed that these compounds accommodate well in the active site of α-glucosidase.

New benzimidazole-oxadiazole derivatives: Synthesis, α-glucosidase, α-amylase activity, and molecular modeling studies as potential antidiabetic agents.

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized with different spectroscopic techniques such as 1 H NMR, 13 C NMR, and HRMS. The synthesized analogs were examined against α-glucosidase and α-amylase enzymes to determine their antidiabetic potential. Compounds 5g and 5q showed the most activity with 35.04 ± 1.28 and 47.60 ± 2.16 µg/mL when compared with the reference drug acarbose (IC50 = 54.63 ± 1.95 µg/mL). Compounds 5g, 5o, 5s, and 5x were screened against the α-amylase enzyme and were found to show excellent potential, with IC50 values ranging from 22.39 ± 1.40 to 32.07 ± 1.55 µg/mL, when compared with the standard acarbose (IC50 = 46.21 ± 1.49 µg/mL). The antioxidant activities of the effective compounds (5o, 5g, 5s, 5x, and 5q) were evaluated by TAS methods. A molecular docking research study was conducted to identify the active site and explain the functions of the active chemicals. To investigate the most likely binding mode of the substances 5g, 5o, 5q, 5s, and 5x, a molecular dynamics simulation was also carried out.

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives containing 1,3-thiazole moiety as potential α‐glucosidase inhibitors

α-Glucosidase, which is involved in the hydrolysis of carbohydrates to glucose and directly mediates blood glucose elevation, is a crucial therapeutic target for type 2 diabetes. In this work, 2,5-disubstituted furan derivatives containing 1,3-thiazole-2-amino or 1,3-thiazole-2-thiol moiety (III-01 ∼ III-30) were synthesized and screened for their inhibitory activity against α-glucosidase. α-Glucosidase inhibition assay demonstrated that all compounds had IC50 in the range of 0.645–94.033 μM and more potent than standard inhibitor acarbose (IC50 = 452.243 ± 54.142 µM). The most promising inhibitors of the two series were compound III-10 (IC50 = 4.120 ± 0.764 μM) and III-24 (IC50 = 0.645 ± 0.052 μM), respectively. Kinetic study and molecular docking simulation revealed that compound III-10 (Ki = 2.04 ± 0.72 μM) is a competitive inhibitor and III-24 (Ki = 0.44 ± 0.53 μM) is a noncompetitive inhibitor against α-glucosidase. Significantly, these two compounds showed nontoxicity towards HEK293, RAW264.7 and HepG2 cells, suggesting that compounds may be considered as a class of potential candidates for further developing novel antidiabetic drugs.

Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies.

A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA (1)) and 11-keto-β-boswellic acid (β-KBA (2)) was designed and synthesized by employing "click" chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate 3 or β-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a-5k in the presence of copper iodide (CuI) and Hünig's base furnished the desired products-1H-1,2,3-triazole hybrids of β-AKBA (6a-6k) and β-KBA (7a-7k)-in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity.

A novel series of benzimidazole ureas 3a-h were elaborated using 2-(1H-benzoimidazol-2-yl) aniline 1 and the appropriate isocyanates 2a-h. The antioxidant and possible antidiabetic activities of the target benzimidazole-ureas 3a-h were evaluated. Almost all compounds 3a-h displayed strong to moderate antioxidant activities. When tested using the three antioxidant techniques, TAC, FRAP, and MCA, compounds 3b and 3c exhibited marked activity. The most active antioxidant compound in this family was compound 3g, which had excellent activity using four different methods: TAC, FRAP, DPPH-SA, and MCA. In vitro antidiabetic assays against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds tested had good to moderate activity. The most favorable results were obtained with compounds 3c, 3e, and 3g, and analysis revealed that compounds 3c (IC50 = 18.65 ± 0.23 μM), 3e (IC50 = 20.7 ± 0.06 μM), and 3g (IC50 = 22.33 ± 0.12 μM) had good α-amylase inhibitory potential comparable to standard acarbose (IC50 = 14.21 ± 0.06 μM). Furthermore, the inhibitory effect of 3c (IC50 = 17.47 ± 0.03 μM), 3e (IC50 = 21.97 ± 0.19 μM), and 3g (IC50 = 23.01 ± 0.12 μM) on α-glucosidase was also comparable to acarbose (IC50 = 15.41 ± 0.32 μM). According to in silico molecular docking studies, compounds 3a-h had considerable affinity for the active sites of human lysosomal acid α-glucosidase (HLAG) and pancreatic α-amylase (HPA), indicating that the majority of the examined compounds had potential anti-hyperglycemic action.

Synthesis and Evaluation of some Novel Triazolo-thiadizoles Derivatives as Anti-diabetic Activity

Triazolo-thiodiazole and related fused heterocyclic compounds are of interest as potential bioactive molecules. Triazolo-thiodiazole derivatives have attracted the attention of organic chemists due to their biological and chemotherapeutic significance. Research in the field of anti-mycobacterium, anti-inflammatory and anti-microbial therapies is ongoing and studies are seeking. Therefore, the discovery of new effective anti-mycobacterium, anti-inflammatory and antimicrobial agents is imperative. The literature survey indicates that the fuse ring of triazolo-thiazazole derivatives has proven to be a good bioactive molecule. They showed various biological activities such as antibacterial, antifungal, anti-inflammatory, tubercular, anticancer, anticonvulsant, antioxidant, analgesic. In view of the above facts it was felt that some were interested in triazo- synthesis. All drugs were screened for their anti-diabetic activity with the standard drug Acarbose by an in vitro alpha-amylation method. The compounds C1 and C3 have been shown to have significant anti-diabetic activity.

Chemical composition, antioxidant, anticholinesterase, and alpha-glucosidase activity of Stevia rebaudiana Bertoni extracts cultivated in Algeria

Stevia rebaudiana Bertoni is an endemic species to Paraguay famous for its sweetening power and therapeutic potential for various diseases such as diabetes. The present work evaluates the chemical composition and antioxidant, anticholinesterase, and α-glucosidase activities of S. rebaudiana. The essential oil (EO) of dry Stevia leaves was analyzed by GC/MS and detected the presence of 33 components. Caryophyllene oxide (24.28%), spathulenol (12.31%) and nerolidol (11.8%), and manool oxide (7.36%) were identified as the major ones. The antioxidant activity was evaluated by four complementary methods: DPPH (2,2 diphenylpicrylhydrazyl, ABTS (2, 2’-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid) free radicals scavenging, Cupric reducing antioxidant capacity (CUPRAC), and reducing power. The crude methanolic extract and its fractions showed a variable antioxidant activity and strongly correlated with the content of quantified bioactive compounds. The ethyl acetate fraction showed a very high antioxidant activity close to the tested standards, while EO was active only in the CUPRAC assy. The petrol ether and chloroform fractions showed the best butyrylcholinesterase (BChE) inhibitory activity with IC50 values: 123.7 ± 1.78 and 170.1 ± 0.78 μg/mL, respectively. On the other hand, EO and chloroform revealed a moderate inhibitory activity against acetylcholinesterase (AChE). The in vitro inhibitory effect of the extracts on α-glucosidase indicated that EO effectively inhibited the enzyme with an IC50: 74.9 ± 6.4 µg/mL, better than the standard acarbose. The EO of Stevia has a significant anti-diabetic potential.

Synthesis and molecular modeling studies of naphthazarin derivatives as novel selective inhibitors of α-glucosidase and α-amylase

Diabetes mellitus is known as one of the most life-threatening diseases and has attracted the attention of medicinal chemists. The design and synthesis of novel potential candidates for the inhibition of α-amylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates are an important approach for the treatment of diabetes. In this current work, a range of novel mono and naphthazarin derivatives were successfully synthesized by the esterification reaction of naphthazarin with different benzoyl chlorides and heterocyclic acyl chlorides. The synthesized compounds were subjected to in vitro antidiabetic activities through α-glucosidase and α-amylase inhibition properties. Despite the limited inhibition potential against α-amylase enzymes, naphthazarin derivatives would be promising targets for antidiabetic study due to the specificity for α-glucosidase enzyme. The compound 18 revealed a dual inhibition behavior, however all the other active compounds were detected as specific for α-glucosidase inhibition and quite potent compared to the standard acarbose which is promising for eliminating the side effects associated with the non-selectivity of acarbose. The compound 19 was the best candidate for inhibition with IC50 value of 7.4 µM and resulted 150-fold better activity compared to the standard. Free energy calculations support the experimental binding affinity of compound 19 found as the most promising drug candidate for α-glucosidase among the synthesized compounds. The plausible binding mode and the interaction of compound 19 complexed with α-glucosidase has been revealed by MD simulations.

Antioxidant and Antidiabetic Properties of Extracts from Three Underutilized Food Plants of North East India.

Three underutilized leafy vegetables Sarcochlamys pulcherrima (Roxb.) Gaudich (SP), Ipomoea aquatica Forssk. (IA) and Zanthoxylum rhetsa (Roxb.) DC (ZR) were extracted with different solvents viz. 95 % ethyl alcohol, methanol and hot water. The extracts were evaluated for their antioxidant potential via DPPH, ABTS and FRAP assay along with electroanalytical studies using cyclic voltammetry. The antidiabetic potential was determined by recording their α-amylase and α-glucosidase inhibitory assay. The total phenolic content (TPC), total flavonoid content (TFC) and the liquid chromatography-mass spectrometry (LC/MS) based phytochemical profiles of the extracts were also determined. All three extracts of SP exhibited significant antioxidant capacity. The antidiabetic potential of the IA and ZR extracts was found to be higher than or at par with that of standard acarbose. LC/MS studies reveal the presence of hitherto reported antioxidant and antidiabetic compounds like gamma-aminobutyric acid, cinnamic acid, caffeic acid, α-viniferin, piperlonguminine, niacin, kaempferol, etc., in the extracts.

In vitro α-glucosidase inhibitory activity of isolated compounds and semisynthetic derivative from aerial parts of Erythrina senegalensis DC

The current study was conducted to isolate the phytoconstituents from Erythrina senegalensis leaves and stem bark and evaluate their inhibitory activity against α-glucosidase, digestive enzyme related to diabetes mellitus. Phytochemical investigation of the leaves resulted in the isolation of three saponins (3–5), two triterpenoids (7 and 8) and two steroids (10a and 10b) as inseparable mixture, while one saponin (6), one triterpenoid (9) and one mixture of two cinnamates (2a and 2b) were isolated from the stem bark. Except for compounds 2 b, 7, 8, 10a and 10 b all the isolated compounds are reported here for the first time from the genus Erythrina. Acetylation of the mixture of two cinnamates (2a and 2b) led to a new diester derivative (1) trivially called erythrinamate. The extracts and pure compounds (3, 4, 6) showed good α-glucosidase inhibitory activity compared to the standard drug acarbose. The findings suggest that saponins of E. senegalensis could be used to develop potential anti-hyperglycemic drugs.

Moxifloxacin Metal Complexes: Synthesis, Characterisation, Antimicrobial and Antidiabetic Activities with Docking Studies

Six new metal complexes of Fe(III), Cu(II), and Hg(II) were synthesised, i.e., three (2, 4, and 5) with moxifloxacin (mono-ligand) and the other three (1, 3 and 6) with moxifloxacin and hydrazine (biligand). These were characterised through UV-Vis, FT-IR, elemental analysis (CHN), atomic absorption spectroscopy, TGA, scanning electron microscopy (SEM), and powder XRD studies. Further, all of these compounds were screened for their antimicrobial, cytotoxic, and antidiabetic potential. The study revealed that the synthesised metal complexes possess an excellent ability to become antifungal agents compared to moxifloxacin. Additionally, the cytotoxicity of compounds 1, 3, and 4 was in the acceptable range with much better antidiabetic potential as compared to the ligand moxifloxacin. Interestingly, the α-amylase inhibition activity of complexes 1 and 3 was found very close to the standard drug acarbose. Furthermore, the computational studies also authenticate the results of the antidiabetic potential of complexes 1, 3, and 4 by presenting the necessary interactions of these compounds with their respective binding sites. The overall results indicate that the antifungal and antidiabetic ability of moxifloxacin is enhanced significantly by complexation with the given metals and the secondary ligand, thereby making it a suitable lead compound for yet another avenue of an antifungal and antidiabetic agent in the field of drug discovery and development.

Synthetic benzofuran-linked chalcones with dual actions: a potential therapeutic approach to manage diabetes mellitus.

Background: Identification of molecules having dual capabilities to reduce postprandial hyperglycemia and oxidative stress is one of the therapeutic approaches to treat diabetes mellitus. In this connection, a library of benzofuran-linked chalcone derivatives were evaluated for their dual action. Methods: A series of substituted benzofuran-linked chalcones (2-33) were synthesized and tested for α-amylase inhibitory as well as2,2-diphenylpicrylhydrazyl (DPPH)and2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)radical scavenging activities. Results: All compounds showed α-amylase inhibitory activity ranging from IC50=12.81±0.03 to 87.17±0.15μM, compared with the standard acarbose (IC50=13.98±0.03μM). Compounds also demonstrated radical scavenging potential against DPPH and ABTS radicals. Conclusion: The identified compounds may serve as potential leads for further advanced research.

Curcumin nanoparticles: physicochemical fabrication, characterization, antioxidant, enzyme inhibition, molecular docking and simulation studies.

Curcumin is an extensively studied natural compound due to its extensive biological applications. However, there are some drawbacks linked to this compound such as poor absorption, low water-solubility, quick systemic elimination, fast metabolism, poor pharmacokinetics, low bioavailability, low penetration targeting efficacy and low stability. To overcome these drawbacks, curcumin is encapsulated in nano-carriers. In the current studies, we synthesized nanoparticles of curcumin without using nanocarriers by different methods such as nano-suspension (Cur-NSM), sonication (Cur-SM) and anti-solvent precipitation (Cur-ASP) to enhance the solubility of curcumin in water. The prepared nanoparticles were characterized by FTIR, SEM and XRD analysis. These curcumin nanoparticles were screened for their solubilities in water, DPPH scavenging, amylase, α-glucosidase and β-glucosidase enzymatic activities. The particle size of nano-curcumin was found to be in the 47.4-98.7 nm range. The reduction in particle size of curcumin dramatically increases its solubility in water to 79.2 μg mL-1, whereas the solubility of curcumin is just 0.98 μg mL-1. Cur-ASP showed the highest free radical scavenging potential (48.84 ± 0.98%) which was comparable with standard BHT (50.48 ± 1.11%) at 75.0 μg mL-1. As well, Cur-ASP showed the highest inhibition of α-amylase (68.67 ± 1.02%), α-glucosidase (58.30 ± 0.52%), and β-glucosidase (64.80 ± 0.43%) at 100 μg mL-1 which is comparable with standard drug acarbose. The greater surface area of nanoparticles exposes the various groups of curcumin for blocking the binding sites of enzymes. This strategy may be helpful in designing curcumin as a potent therapeutic agent against diabetes mellitus. Further, the molecular interactions of curcumin with α-amylase, α-glucosidase, β-glucosidase, and polyphenol oxidase were assessed by analyzing the plausible binding modes of curcumin in the binding pocket of each receptor. The best binding mode of curcumin was used to make complexes with the target proteins and their stability was confirmed by 50 ns MD simulation.

Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study

With the increasing global burden of diabetes mellitus type 2, the search for the new drugs, with better pharmacological profile is continued. As a part of this surge, the synthesis, pharmacological in vitro and computational evaluation of five, simple carbamate derivatives, against carbohydrate digestive enzyme ?-glucosidase, is disclosed herein. Results of the experimental and computational assessment indicated that examined carbamates deterred the activity of ?-glucosidase with acceptable IC50 values ranging from 65.34 to 79.89 ?M compared to a standard drug acarbose (109.71 ?M). Similarly, the studied compounds displayed in silico binding affinity for ?-glucosidase enzyme with significant binding energies. Preliminary toxicity profiles of studied carbamates against three cancerous cell lines indicated their poor activity, suggesting that significant structural modifications have to be made to improve their anticancer efficiency. Results of the present study indicate that the examined carbamates were able to virtually or experimentally interact with an important target of diabetes mellitus type 2. Additionally, a new pharmacophore model is proposed featuring hydrogen bond donating carbamate ?NH group, hydrogen bond accepting carbamate ?OCH3 group and hydrophobic stabilization of aromatic moieties.

Novel hybrids of thiazolidinedione-1,3,4-oxadiazole derivatives: synthesis, molecular docking, MD simulations, ADMET study, in vitro, and in vivo anti-diabetic assessment.

As compared to standard medicinal compounds, hybrid molecules that contain multiple biologically active functional groups have greater affinity and efficiency. Hence based on this concept, we predicted that a combination of thiazolidinediones and 1,3,4-oxadiazoles may enhance α-amylase and α-glucosidase inhibition activity. A series of novel 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)thiazolidine-2,5-dione derivatives (5a-5j) were synthesized and characterized using different spectroscopic techniques i.e., FTIR, 1H-NMR, 13C-NMR and MS. To evaluate in silico, molecular docking, MMGBSA, and MD simulations were carried out which were further evaluated via in vitro inhibition of α-amylase and α-glycosidase enzyme inhibition assays. In addition, the in vivo study was performed on a genetic model of Drosophila melanogaster to assess the antihyperglycemic effects. The compounds (5a-5j) demonstrated α-amylase and α-glucosidase inhibitory activity in the range of IC50 values 18.42 ± 0.21-55.43 ± 0.66 μM and 17.21 ± 0.22-51.28 ± 0.88 μM respectively when compared to standard acarbose. Based on the in vitro studies, compounds 5a, 5b, and 5j were found to be potent against both enzymes. In vivo studies have shown that compounds 5a, 5b, and 5j lower glucose levels in Drosophila. These compounds could be further developed in the future to produce a new class of antidiabetic agents.

In Vitro Evaluation of Alpha-amylase Inhibition, Antioxidant Potential and Phytochemical Analysis of Acacia Modesta

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which affects insulin secretion. Among several approaches to treat diabetes, controlling postprandial hyperglycemia is an effective way to manage diabetes type II. In this regard, medicinal plants are considered the best source of new chemical entities with fewer side effects. This study aims to evaluate the alpha-amylase inhibitory potential of Acacia modesta ethanol and aqueous extracts in correlation with its antioxidant potential and develop an anti-diabatic drug against the alpha-amylase enzyme that can control the post-prandial hyperglycemia. We used the starch-iodine color change method for α-amylase, a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay for determining the antioxidant potential and determined different phytochemicals, including phenols, flavonoids, and tannins by spectrophotometry. The results indicated that the gum of A. modesta possesses potent α-amylase inhibitory potential with IC 50 values of 100.4 ± 0.04 µg/mL in ethanol and 91.8 ± 0.05 µg/mL in the aqueous extract, which was approximately 3-folds higher compared to standard acarbose (286.8 ± 0.04 µM). The antioxidant activity was also higher in gum compared to any other part. As for phytochemical analysis, this plant possesses higher amounts of tannins and phenols, while flavonoids are in lesser amounts. The gum of A. modesta shows a dual mode of action, i.e., antioxidant and amylase inhibitor, which makes it a better candidate for diabetes management. The novelty is that, to our knowledge, this study is the first to report the anti-diabetic and antioxidant properties of A. modesta using pancreatic amylase as a drug target from Khyber Pakhtunkhwa, Pakistan. Keywords: Acacia modesta , alpha-amylase, flavonoids, tannins, antioxidant. https://doi.org/10.55463/issn.1674-2974.50.2.30

SELECTED TRADITIONAL MEDICINAL PLANTS TO REDUCE POST-PRANDIAL HYPERGLYCAEMIA: AN IN VITRO SCREENING

The present study is focussed on an in vitro approach to evaluate the antidiabetic potential of some selected traditional medicinal plants used by traditional practitioners of South India for curing hyperglycaemia. The study emphasized on the potential of the extracts to reduce post-prandial glucose levels through inhibition of carbohydrate hydrolyzing enzyme, α-amylase and its mode of inhibition. Four different solvent fractions (Petroleum ether fraction, Chloroform fraction, Ethyl acetate fraction and 80% methanolic fraction) of extracts of shoots of Tinospora crispa (L) Hook.f. and Thomson, denoted as PE TC, CH TC, EA TC, 80%M TC and roots of Anacardium occidentale L, denoted as PE AO, CH AO, EA AO and 80%M AO were selected for antidiabetic screening. Phytochemical profiling of the extracts revealed that the all of the eight extracts were a rich repository of secondary metabolites. Ensuing to standard acarbose drug (IC50 value = 0.19 mg/mL), PE TC (IC50 value =1.49 mg/mL) outperformed among the fractions evaluated to exhibit an uncompetitive mode of inhibiting the α-amylase enzyme. 80%M AO, CH AO too exhibited substantial inhibitory activity on the enzyme followed by CH AO that showed a mixed inhibitory response. Remaining fractions remained uncompetitive. All the extracts exhibited potential antioxidant activity, 80% M AO being the best with an IC50 value of 0.026 mg/mL followed by EA AO (IC50 value =0.031 mg/mL). The cytotoxicity assay of the extracts on the MIN6 pancreatic cell lines revealed all the extracts to be least cytotoxic. Thus, PE TC and 80%M AO offers to be promising lead candidates to be developed as an efficient antidiabetic agents for post-prandial hyperglycaemia.