Standard Acarbose Research Articles

Synthesis of New Indole‐Based Thiazole Derivatives as Potential Antiglycation and Anti α‐Glucosidase Agents: In Vitro and In Silico Studies

AbstractDiabetes mellitus is a metabolic disease, characterized by the elevated levels of blood glucose, known as hyperglycemia. It is one of the serious health challenges, and is rapidly becoming a significant cause of morbidity, and mortality, worldwide. The persistent hyperglycemic state in diabetes mellitus leads to the formation of advanced glycation end products (AGEs), which is identified as a key factor involved in the progression of diabetes, and diabetes‐associated late complications. keeping in view the medicinal properties of indole, and thiazole, in the present study, novel indole‐based thiazoles (1–26) were synthesized, and evaluated for their in vitro α‐glucosidase, and antiglycation activities. These indole‐based thiazoles were characterized from their spectral data. All these compounds showed moderate to excellent antiglycation activity (IC50 between 642.2±0.013 to 46.93±0.003 μM) including compounds 17, 20, 22–26 which showed a significant antiglycation activity as the reference molecule, rutin (IC50=56±0.008 μM) used as standard. Further, these derivatives exhibited significant α‐glucosidase inhibition activity (P<0.001) with IC50 in the range of 111.8±0.9001 and 666.5±1.0111 μM (standard drug acarbose: IC50=855.8±1.2001 μM). Binding interactions of these compounds with α‐glucosidase enzyme were studied in silico, which showed strong correlation with the experimental data. Inhibition of α‐glucosidase enzyme, and AGEs formation by these compounds suggest them as promising scaffolds for further studies.

Salazinic Acid and Norlobaridone from the Lichen Hypotrachyna cirrhata: Antioxidant Activity, α-Glucosidase Inhibitory and Molecular Docking Studies

The present study was intended for the identification of secondary metabolites in acetone extract of the lichen Hypotrachyna cirrhata using UPLC-ESI-QToF-MS/MS and the detection of bioactive compounds. This study led to the identification of 22 metabolites based on their MS/MS spectra, accurate molecular masses, molecular formula from a comparison of the literature database (DNP), and fragmentation patterns. In addition, potent antioxidant and α-glucosidase inhibitory potentials of acetone extract of H. cirrhata motivated us to isolate 10 metabolites, which were characterized as salazinic acid (11), norlobaridone (12), atranorin (13), lecanoric acid (14), lichesterinic acid (15), protolichesterinic acid (16), methyl hematommate (17), iso-rhizonic acid (18), atranol (19), and methylatratate (20) based on their spectral data. All these isolates were assessed for their free radicals scavenging, radical-induced DNA damage, and intestinal α-glucosidase inhibitory activities. The results indicated that norlobaridone (12), lecanoric acid (14), methyl hematommate (17), and atranol (19) showed potent antioxidant activity, while depsidones (salazinic acid (11), norlobaridone (12)) and a monophenolic compound (iso-rhizonic acid, (18)) displayed significant intestinal α-glucosidase inhibitory activities (p < 0.001), which is comparable to standard acarbose. These results were further correlated with molecular docking studies, which indicated that the alkyl chain of norlobaridione (12) is hooked into the finger-like cavity of the allosteric pocket; moreover, it also established Van der Waals interactions with hydrophobic residues of the allosteric pocket. Thus, the potency of norlobaridone to inhibit α-glucosidase enzyme might be associated with its allosteric binding. Also, MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energies of salazinic acid (11) and norlobaridone (12) were superior to acarbose and may have contributed to their high activity compared to acarbose.

Synthesis, biological evaluation and molecular docking study of indazole based schiff base analogues as new anti-diabetic inhibitors

Indazole-based Schiff base analogues (1–27) were synthesized by a three-step reaction pathway starting from 1-methyl-1H-indazole-3-carboxylic acid as the basic compound. The structure of the new indazoles was characterized and confirmed by mass spectral analyses as well as NMR spectroscopic data. All synthesized analogues were screened for their in vitro α-glucosidase and α-amylase inhibitory activities. All analogues of the series exhibited good inhibitory potentials, with IC50 values ranging from 0.40 ± 0.01 to 16.20 ± 0.30 µM for α-glucosidase and 0.70 ± 0.01 to 17.40 ± 0.30 µM for α-amylase as compared to the standard drug acarbose (IC50 = 12.90 ± 0.10 and 12.80 ± 0.10 µM, respectively). The most effective analogue of the series is analogue 22 having 3‑hydroxyl groups with an IC50 value of 0.40 ± 0.01 µM and 0.70 ± 0.01 µM for α-glucosidase and α-amylase, respectively. Structure-activity relationship was carried out, which mainly depends upon the nature, number, position, and electron donating/withdrawing effect of the substituent(s) attached to the phenyl ring. To investigate the binding interaction of the potent analogue with the active site of an enzyme, molecular docking studies were carried out.

The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline-Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents.

In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (1-17) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (1-17) were characterized using a combination of several spectroscopic techniques, including FT-IR, 1H-NMR, 13C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against α-glucosidase and urease enzymes. These analogues disclosed varying degrees of α-glucosidase and urease inhibitory activities, with their IC50 values ranging from 2.50 to 17.50 μM (α-glucosidase) and 14.30 to 41.50 (urease). Compounds 6, 7, 14, and 12, with IC50 values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC50 = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC50 = 31.40 μM), respectively, showed excellent inhibitory activity. The structure-activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound 6 was a dual potent inhibitor against α-glucosidase and urease due to the presence of -CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC50 values. Moreover, in silico studies on most active compounds, i.e., 6, 7, 14, and 12, were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

BackgroundNovel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. ObjectiveSynthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. MethodThiosemicarbazone derivatives (4–13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4–13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. ResultsThe synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

In-vitro Antidiabetic Activity of Xanthium strumarium L. Leaves

Diabetes mellitus has become a major public health and economic problem across the globe. The inadequacies, as well as serious adverse effects associated with conventional medicines, led to a determined search for alternative natural therapeutic agents. This study aimed to evaluate the in-vitro antidiabetic effects of Xanthium Strumarium L. Leaves Extracts. The % yield of acetone and ethyl acetate extract was found to be 1.9% and 2.5% respectively. Qualitative phytochemical tests confirmed the presence of alkaloids, glycosides, saponins, fats and oils, and phenols in acetone extract while alkaloids, glycosides, glycosides, saponins, steroids and phenols were present in ethyl acetate extract. The in-vitro antidiabetic and antioxidant studies of the extract revealed that the ethyl acetate extract of Xanthium strumarium L. leaves showed good antidiabetic and antioxidant potential when compared with acetone extract and significant with standard compound Acarbose.

Cu(II) coordination polymers based on 1,3,5-tris(triazol-1-ylmethyl)-2,4,6-trimethylbenzene: synthesis, structure, and biological properties

Two new Cu(II)-based coordination polymers, [Cu(TTTMB)(Hbtrc2−)]n (1) and {[Cu(TTTMB)2(H2O)2](NO3)2(H2O)4}n (2), were synthesized under hydrothermal conditions (TTTMB = 1,3,5-tris(triazol-1-ylmethyl)-2,4,6-trimethylbenzene; H3btrc = 1,3,5-trimesic acid). The structures of these polymers were established by elemental analysis, IR, and single-crystal X-ray diffraction analysis. Polymer 1 displays a three-dimensional (3-D) structure with the Schläfli symbol (4·62)(4·67·82) and crystallizes in the monoclinic space group P2(1)/n. Each Cu(II) in 1 is five-coordinate in a slightly distorted rectangular pyramid geometry. Polymer 2 has a 2-D network structure with (4,4) topology and each Cu(II) ion has a slightly distorted octahedral coordination geometry. The antidiabetic activity against α-amylase and antioxidant activity against DPPH of the two Cu(II)-based complexes were evaluated in vitro. Polymers 1 (IC50 = 1.43 mg/mL) and 2 (IC50 = 2.45 mg/mL) exhibited more effective inhibition on α-amylase than the standard drug acarbose (IC50 = 2.94 mg/mL). The results of the antioxidant studies revealed that 2 demonstrated a potent scavenging effect on DPPH with IC50 values of 2.59 mg/mL, slightly lower than that of vitamin E (2.67 mg/mL).

In Vitro and In Silico Evaluation of Amylase, Tyrosinase, and Pancreatic Lipase Inhibitions of Novel Benzothiazole‐Sulfonate Derivatives

AbstractThis paper provides a comprehensive account of the synthesis and assessment of newly developed aryl sulfonate derivatives based on benzothiazole as enzyme inhibitors, specifically focusing on their ability to target tyrosinase, amylase, and pancreatic lipase. The assessments were performed utilizing experimental (in vitro) and computational (in silico) methodologies. For this aim, nine different aryl sulfonate derivatives were synthesized. The synthesized compounds were subjected to structural characterizations by utilizing Nuclear Magnetic Resonance (1H NMR, 13C NMR) and High‐Resolution Mass Spectrometry (HRMS) studies, which provided confirmation of their structural properties. The inhibitory efficiency of the compounds was determined by measuring their 50 % inhibitory concentration (IC50) values and comparing them with the standard inhibitory compounds. According to the in vitro amylase activity, benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate showed the best inhibition with the lowest IC50 value (43.31±4.3 μM) which was calculated to be at a close level to the IC50 value of standard acarbose (38.50±3.8 μM). Also, benzo[d]thiazol‐2‐yl 4‐bromobenzenesulfonate (22.73±4.15 μM) and benzo[d]thiazol‐2‐yl 4‐chlorobenzenesulfonate (25.28±1.95 μM) were calculated to have the lowest IC50 values and the most effective inhibition capacities against pancreatic lipase. Benzo[d]thiazol‐2‐yl 4‐fluorobenzenesulfonate and benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate significantly exhibited superior tyrosinase inhibition compared to other derivatives and conventional kojic acid. In silico molecular docking affirmed that benzo[d]thiazol‐2‐yl naphthalene‐2‐sulfonate presented the highest binding affinities to the studied enzymes, with values of −7.8 kcal/mol for tyrosinase, −10.7 kcal/mol for pancreatic lipase, and −9.4 kcal/mol for α‐amylase. The pharmacokinetic characteristics and drug‐likeness of the synthesized sulfonate derivatives were also evaluated using absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Density Functional Theory (DFT) calculations were employed at the DFT/B3LYP/6‐311 g(d,p) level of theory to investigate the electronic characteristics of the compounds, therefore facilitating the comprehension of the reported enzyme inhibitory actions. In summary, our research highlights the potential of benzothiazole aryl sulfonate derivatives as effective enzyme inhibitors that hold promise for therapeutic applications.

Chitosan Nanoparticles for Enhanced Delivery of Sida cordifolia Extract: Formulation, Optimization and Bioactivity Assessment.

In a continuous search for an essential antidiabetic agent, Sida cordifolia hydroalcoholic (SCHA) extract-loaded chitosan nanoparticles (SCHA-CS-NP) were optimized. The Box-Behnken design (BBD Design-Expert software, version 14) with three parameters was used to optimize the nanoparticles after creating them using the ion gelation method. The chitosan and Tween 20 contents and the stirring speed were chosen as the independent variables, and their separate and combined effects on particle size (Y1), polydispersity index (Y2) and entrapment efficiency (Y3) were observed. The optimized formulation showed a particle size of 51 nm, an entrapment efficiency of 84.54% and a polydispersity index of 0.391. Physicochemical characterization, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), a drug release study, an ex vivo permeation study, and an antioxidant study were performed. Confocal laser scanning microscopy (CLSM) images demonstrated that chitosan nanoparticles loaded with rhodamine B-laden SCHA extract had superior penetration compared to the control (rhodamine B solution). Furthermore, compared to conventional ascorbic acid (IC50 = 45 µg/mL), a superior antioxidant activity was discovered for SCHA-CS-NPs (IC50 = 86.45 ± 2.24 µg/mL), while SCHA-CS-NPs also exhibited strong antidiabetic potential (IC50 = 93.71 ± 1.79 µg/mL) compared to standard acarbose (IC50 = 97.25 ± 1.43 µg/mL). The overall results demonstrated that SCHA-CS-NPs are a promising and efficient formulation for oral delivery.

Synthesis of novel coumarin-based thiosemicarbazones and their implications in diabetic management via in-vitro and in-silico approaches

Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a–3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.

Multitargeted inhibition of key enzymes associated with diabetes and Alzheimer's disease by 1,3,4-oxadiazole derivatives: Synthesis, in vitro screening, and computational studies.

A library of 22 derivatives of 1,3,4-oxadiazole-2-thiol was synthesized, structurally characterized, and assessed for its potential to inhibit α-amylase, α-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and antioxidant activities. Most of the tested compounds demonstrated good to moderate inhibition potential; however, their activity was lower than that of the standard acarbose. Significantly, compound 3f exhibited the highest inhibition potential against α-glucosidase and α-amylase enzymes, with IC50 values of 18.52 ± 0.09 and 20.25 ± 1.05 µM, respectively, in comparison to the standard acarbose (12.29 ± 0.26; 15.98 ± 0.14 µM). Compounds also demonstrated varying degrees of inhibitory potential against AChE (IC50 = 9.25 ± 0.19 to 36.15 ± 0.12 µM) and BChE (IC50 = 10.06 ± 0.43 to 35.13 ± 0.12 µM) enzymes compared to the standard donepezil (IC50 = 2.01 ± 0.12; 3.12 ± 0.06 µM), as well as DPPH (IC50 = 20.98 ± 0.06 to 52.83 ± 0.12 µM) and ABTS radical scavenging activities (IC50 = 22.29 ± 0.18 to 47.98 ± 0.03 µM) in comparison to the standard ascorbic acid (IC50 = 18.12 ± 0.15; 19.19 ± 0.72). The kinetic investigations have demonstrated that the compounds exhibit competitive-type inhibition for α-amylase, noncompetitive-type inhibition for α-glucosidase and AChE, and mixed-type inhibition for BChE. Additionally, a molecular docking study was performed on all synthetic oxadiazoles to explore the interaction details of these compounds with the active sites of the enzymes.

Stereoselective Synthesis of Highly Functionalized Aminobenzothiazole-Fused Spirooxindole Derivatives: in silico and in vitro Anti-Diabetic Studies

AbstractA series of highly functionalized spirooxindole pyrro­lizidine/pyrrolothiazole derivatives have been synthesized by the three-component 1,3-dipolar cycloaddition reaction of benzothiazolyl amides with isatin-based azomethine ylides. The pharmacologically significant spirooxindole derivatives bearing one quaternary carbon and four stereocenters were obtained in excellent yields (up to 93%). The compounds were screened for their anti-diabetic activity against two enzymes, α-glucosidase and α-amylase. The results exhibited potent inhibitory activity against these enzymes, especially N-(benzo[d]thiazol-2-yl)-5-fluoro-2-oxo-7′-phenyl-1′,6′,7′,7a′-tetrahydro-3′H-spiro[indoline-3,5′-pyrrolo[1,2-c]thiazole]-6′-carboxamide (6b), which showed excellent activity compared to the standard acarbose. Molecular docking against the receptors showed excellent interactions of the synthesized compounds in a similar way to acarbose. Further, the docking results of the spirooxindole pyrrolothiazole (6b) evinced the strong binding interactions of the compound with the receptors. Additionally, molecular dynamics simulations were carried out and confirmed the stability of the spirooxindole pyrrolothiazole (6b) in the active pockets of enzymes over 100 ns.

Essential Oils of Alpinia vietnamica Rhizomes and Leaves: Chemical Composition, Cytotoxicity, α-Glucosidase Inhibition, and Molecular Docking Approach

Objective: Alpinia is a big genus of flowering plants in the family Zingiberaceae. The plants of this genus are generally aromatic due to their essential oils. The current study aims to identify chemical compositions in the rhizome and leaf oils of Alpinia vietnamica H.Đ. Trần, Luu & Škorničk. Methods: Essential oils of A vietnamica rhizomes and leaves obtained by hydrodistillation were investigated by the gas chromatography–flame ionization detection/mass spectrometry (GC–FID/MS) analysis. A vietnamica essential oils have been subjected to cytotoxic and α-glucosidase inhibitory assays. The protein interactions of the major compounds were viewed by molecular docking study. Results: In general, monoterpene hydrocarbons (60.4%-62.5%) and their oxygenated derivatives (18.1%-29.0%) were the main chemical classes of the rhizome and leaf oils. In the meantime, 1,8-cineole (25.7%-29.0%), β-pinene (12.8%-21.3%), geraniol (9.0%-15.2%), and α-pinene (6.1%-7.5%) can be seen as the main compounds. A vietnamica essential oils showed cytotoxicity toward four cancer cell lines KB, Hep-G2, Lu-1, and MCF-7 with IC50 values of 82.39 to 254.1 µg/mL. Significantly, the leaf oil (IC50 115.18 µg/mL) was better than the standard compound acarbose (IC50 156.68 µg/mL) in the α-glucosidase inhibitory assay. The results of molecular docking simulation suggested that 1,8-cineole, geraniol, α-pinene, and β-pinene could generate a similar inhibition (binding affinities) with acarbose, and the hydrogen and hydrophobic interactions played contributory roles in the binding to α-glucosidase enzyme. Conclusion: Further phytochemical investigations on this species, especially chromatographic separations to isolate bioactive metabolites, are needed. As well, pharmacological experiments are welcome since the current study is the first result.

Diyarbakır/Türkiye’nin Altı Farklı Bölgesinden Toplanan Matricaria chamomilla L. Örneklerinin Kamazulen İçeriği ve Hipoglisemik Potansiyeli

Chamomile (Matricaria chamomilla L.) is one of the oldest and most widely known medicinal plants belonging to Asteraceae family. An artifact named chamazulene forms from the sesquiterpene structured lactones such as matricin during the hydro-distillation of flowering tops of chamomile. These compounds are associated with the anti-inflammatory potential of chamomile along with flavonoids, other sesquiterpenoids, and essential oil of the plant. However, not all M. chamomilla specimens grown in different regions or species known and used as chamomile contains sesquiterpene lactone components. Thus, chamazulene content of chamomile has become a pharmaceutical interest. A traditional and well-established indication of the plant is diabetes. Protective and beneficial effects of chamomile on diabetic complications and glycemic control have been proposed by several studies. However, the mechanism of action is yet to be elucidated. Flowering tops of chamomile samples were collected from six different localities of Diyarbakır/Türkiye. Essential oils (EOs) were obtained by hydro-distillation. Petroleum ether (PE), ethyl acetate (EA), methanol (Me), and infusion (INF) extracts were prepared. Qualitative analysis of the EOs resulted in no chamazulene content. Bismil district might be eligible for medicinal chamomile culture with its high essential oil yield. In-vitro hypoglycemic potentials of the extracts and EOs were evaluated by α-glucosidase inhibitory assay. All EOs and EA extracts (except M4-Bismil samples) showed the highest inhibitory activities comparable to that of standard acarbose. α-Glucosidase inhibition might be a significant mechanism of action contributing to the antidiabetic effects of chamomile.

A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 μM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

Pharmacognostical and Pharmacological Evaluation of leaves of Citrullus lanatus L.

Citrullus lanatus (Watermelon) is commonly available throughout India and traditionally used in treatment of various ailments. This plant is well-explored for its fruit but the potential of its leaves is still unexplored. Thus, the present study focuses on pharmacognostical and pharmacological evaluation of leaves of Citrullus lanatus. In pharmacognostical evaluation, all macroscopic, microscopic, qualitative, quantitative and microbiological analysis were performed. In pharmacological evaluation, the study mainly focuses on the potential of leaves for antioxidant and antidiabetic activities. The antioxidant activity has been performed by various methods such as DPPH and phospho-molybdenum method. The antidiabetic activity has been performed by non-enzymatic glycosylation of hemoglobin assay method, glucose uptake in yeast cells method, alpha amylase inhibition assay method and alpha glucosidase inhibition assay method. The results of antioxidant activity shows that the plant extract possess good free radical scavenging properties due to the presence of vitamin C, polyphenol and flavonoid content. The results of antidiabetic activity by non-enzymatic glycosylation method shows that the plant extract of C. lanatus exhibit significant inhibition of glycosylation as compared with standard drug alpha tocopherol. In glucose uptake by yeast cells method, the extract showed greater efficiency in increasing the glucose uptake by yeast cells as compared to standard drug acarbose. In alpha amylase inhibition method, Alpha amylase inhibitors bind to alpha bond of polysaccharide and prevent breakdown of polysaccharide in mono and disaccharide which shows significant activity of plant extract as compared to an acarbose standard drug. Thus from the above findings, it can be concluded that C. lanatus leaves possess a great potential for antioxidant and antidiabetic activity and this plant should be more researched and formulation should be marketed in the recent future.
 Keywords: Citrullus lanatus (Cucurbitaceous), Watermelon, Anti-oxidant Activity, Anti-diabetic Activity

Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of β-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity.

The major cause of hyperglycemia can generally be attributed to β-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of β-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (β-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with β-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against β-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the β-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

Discovery of novel 4,5-diphenyl-imidazol-α-aminophosphonate hybrids as promising anti-diabetic agents: Design, synthesis, in vitro, and in silico enzymatic studies

Herein, a novel series of 4,5-diphenyl-imidazol-α-aminophosphonate hybrids 4a-m was designed, synthesized, and evaluated as new anti-diabetic agents. These compounds were evaluated against two important target enzymes in the diabetes treatment: α-glucosidase and α-amylase. These new compounds were synthesized in three steps and characterized by different spectroscopic techniques. The in vitro evaluations demonstrated that all the synthesized compounds 4a-m were more potent that standard inhibitor acarbose against studied enzymes. Among these compound, the most potent compound against both studied enzymes was 3-bromo derivative 4l. The latter compound with IC50 = 5.96 nM was 18-times more potent than acarbose (IC50 = 106.63 nM) against α-glucosidase. Moreover, compound 4l with IC50 = 1.62 nM was 27-times more potent than acarbose (IC50 = 44.16 nM) against α-amylase. Molecular docking analysis revealed that this compound well accommodated in the binding site of α-glucosidase and α-amylase enzymes with notably more favorable binding energy as compared to acarbose.

Isolation of new bibenzyl derivatives from Bulbophyllum auricomum and evaluation of their α-glucosidase inhibitory activity

Bulbophyllum auricomum Lindl., commonly referred to as the 'Royal Thazin' in Myanmar, holds the esteemed status of being the national flower of the country. In our research, we delved into the ethyl acetate extract derived from the pseudobulbs and roots of this plant. This extract exhibited significant inhibitory activity against the α-glucosidase enzyme, prompting a detailed investigation into its active compounds. Our study resulted in the isolation and characterization of several compounds, including a novel natural product named 2-(4-hydroxyphenyl) ethyl 3-(2-hydroxyphenyl) propanoate. Additionally, we identified two previously unreported inseparable isomeric bibenzyls, namely 7-hydroxybatatasin III and 8-hydroxybatatasin III. Furthermore, we isolated six known compounds, including batatasin III, lusianthridin, tristin, phochinenin G, phoyunnanin E, and phoyunnanin C. Significantly, our study unveiled that phochinenin G acts as a reversible noncompetitive inhibitor of the α-glucosidase enzyme. This compound displayed greater inhibitory activity than the standard drug acarbose.

Diphenyl-substituted triazine derivatives: synthesis, α-glucosidase inhibitory activity, kineticsand in silico studies.

Background: Diabetes mellitus (DM) is a chronic disorder, considered to be a major global health challenge in the 21st century. α-Glucosidase enzyme is a well-known drug target to treat Type II DM. Methods: A new library of biphenyl-substituted triazines was synthesized and confirmed by various spectroscopic techniques. Results: All compounds showed potent α-glucosidase inhibitory activity, with IC50 values ranging from 35.35±0.34 to 564.41±0.91μM, as the standard acarbose, IC50 value of 750.7±0.13μM. Our in silico study has predicted key interactions with the enzyme's active site. Drug-likeness and absorption, distribution, metabolism, excretionand toxicitywere also studied. Conclusion: This study has identified a range of potential hits against theα-glucosidase enzyme that may serve as antidiabetic agents after further investigations.