Query: antidiabetic molecular docking

title: Predicting ADME and Molecular Docking Analysis of Andrographis paniculata and Strobilanthes crispus Chemical Constituents Againts Antidiabetic Molecular Targets
abstract: Andrographis paniculata and Strobilanthes crispus are two medicinal plants from Acanthaceae family, known to have antidiabetic activity. This study aimed to investigate the molecular interaction of A. paniculata and S. crispus phytochemical constituents with various macromolecular targets of antidiabetic agent through molecular docking. Nineteen A. paniculata and twenty S. crispus chemical constituents were docked to four macromolecular targets of antidiabetic agent by using AutoDock Vina in PyRx. The results revealed that compounds from A. paniculata that have the best binding affinity protein targets was 19 tripenhyl isoandrographolide to glucokinase 10.4 kcal/mol) Dipeptidyl peptidase 4 (DPP4) (9.3 kcal/mol) and a glucosidase 8.8 kcal/mol) and andrographolactone to Protein Tyrosin Phosphatase1B (PTP1B) 9.5 kcal/mol) Whereas compounds in the S. crispus derivatives that have the best binding affinity were stigmasterol to glucokinase 9.9 kcal/mol) rutin to DPP4 9.7 kcal/mol) lupeol to a glucosidase 8.8 kcal/mol) and luteolin to PTP1B 8.8 kcal/mol) The differences between the two plants were due to the differences in compounds in each of the plants as well as differences in target proteins. Other than that, profile of absorption, distribution, metabolism, and excretion (ADME) predictions are very important because they play a critical role in assessing the quality of potential clinical candidates for a new drug. Compounds with best binding energy that showed good ADME properties were andrographolactone, stigmasterol, lupeol and luteolin. Deoxyandrographolide was predicted to have the best ADME properties, however its affinity to target proteins was lower than native ligands.

title: DOCKING STUDIES ON ANTIDIABETIC MOLECULAR TARGETS OF PHYTOCHEMICAL COMPOUNDS OF SYZYGIUM CUMINI (L. SKEELS
abstract: Different parts of jamun tree (Syzygium cumini L. skeels) which belongs to the family Myrtaceae are well known for their antidiabetic activity. Traditional practitioners in India are using the leaf, bark, and fruits of this medicinal plant over many centuries to manage the diabetic patients. Although several research works have been conducted to prove the efficacy of this plant extracts and also to explore the active principles of this plant drug, there is no information regarding the interaction of phytoconstituents of jamun tree with diabetic targets at the molecular level. Hence, this study focused to apply a computational approach to reveal the interaction of molecules of jamun tree with antidiabetic targets.  Lamarckian genetic algorithm methodology was used for docking of 22 phytoconstituents with a amylase, a key enzyme that involved in carbohydrate metabolism using Autodock software.  Analysis of binding energy of ligands with target receptors was remarkably lower especially for friedelin 9.54 kcal/mol) epifriedelanol 8.98 kcal/mol) betulinic acid 8.60 kcal/mol) beta sitosterol 8.56 kcal/mol) petunidin 3 gentiobioside 7.52 kcal/mol) kaempferol 7.08 kcal/mol) petunidin 6.21 kcal/mol) quercetin 6.03 kcal/mol) myricetin 5.80 kcal/mol) and bergenin 5.27 kcal/mol) when compared to the synthetic drug acarbose 2.43 kcal/mol)  Potential molecules identified from this study could be considered as a lead to design/synthesize anti diabetic drug molecules in pharmaceutical industry.  Jamun tree, Syzygium cumini, Phytochemicals, Diabetes, a amylase, Molecular docking.

title: Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies.
abstract: A new method of obtaining multifunctional pyrazoles by the reaction of 1,3 dipolar addition of tribenzylsulfonyliminochloride to polarophiles has been developed. This imine is obtained by reacting tribenzylamine with N chlorobenzene sulfamide (chloramine B) Regardless of the structure and composition of polarophiles, the cyclization reaction takes place in the presence of alkali in 6 8 h of boiling, which proves the activation of the methylene groups of tribenzylamine using the electron withdrawing sulfonamide group. These novel derivatives were effective inhibitors of the a glycosidase, butyrylcholinesterase (BChE) and acetylcholinesterase enzymes (AChE) with Ki values in the range of 0.45 0.08 1.24 0.27 uM for a glycosidase, 6.04 0.95 11.61 2.84 uM for BChE, and 2.04 0.24 4.23 1.02 uM for AChE, respectively. The biological activities of the studied molecules against enzyme molecules were investigated by molecular docking calculations. The enzymes studied were AChE for ID 4M0E, BChE for ID 5NN0 BChE, and a Glycosidase for ID 1XSI (a Gly) respectively.

title: Synthesis, in vitro a glucosidase inhibition, antioxidant, in vivo antidiabetic and molecular docking studies of pyrrolidine 2,5 dione and thiazolidine 2,4 dione derivatives.
abstract: a Glucosidase is considered as a therapeutic target for the treatment of type 2 diabetes mellitus (DM2) In current study, we synthesized pyrrolidine 2,5 dione (succinimide) and thiazolidine 2,4 dione derivatives and evaluated for their ability to inhibit a Glucosidase. Pyrrolidine 2,5 dione derivatives (11a o) showed moderate to poor a glucosidase inhibition. Compound 11o with the IC50 value of 28.3 0.28 uM emerged as a good inhibitor of a glucosidase. Thiazolidine 2,4 dione and dihydropyrimidine (TZD DHPM) hybrids (22a c) showed excellent inhibitory activities. The most active compound 22a displayed IC50 value of 0.98 0.008 uM. Other two compounds of this series also showed activity in low micromolar range. The in vivo antidiabetic study of three compounds 11n, 11o and 22a were also determined using alloxan induced diabetes mice model. Compounds 11o and 22a showed significant hypoglycemic effect compared to the reference drug. In vivo acute toxicity study showed the safety of these selected compounds. In silico docking studies were carried out to rationalize the in vitro results. The binding modes and bioassay results of TZD DHPM hybrids showed that interactions with important residues appeared significant for high potency.

title: Molecular Docking and Pharmacological Property Analysis of Antidiabetic Agents from Medicinal Plants of Bangladesh against Type II Diabetes: A Computational Approach
abstract: Diabetes Mellitus (DM) is a metabolic disorder which affects the people of almost all ethnic groups around the world severely. The effect of this disease involves lifelong suffering and has no permanent cure till now. Although different medications are available in the market but they are not accessible to every person due to their high cost, requirement of frequent administration and inability to alleviate diabetes permanently. Plant derived compounds are being commonly used by many people, specifically by those in rural areas of many countries as ayurvedic source of antidiabetic agents and these are more preferable to everyone due to their less toxicity and side effects. These compounds work by variety of mechanisms which involve different interactions between effective compounds and target proteins in the metabolic pathway. Molecular docking study helps in determining the interaction between specific ligands and receptors to specify the best lead that fits the target. This study has been designed to investigate the interactions with the aid of computational simulation tool between medicinal plant derived antidiabetic agents (Aegeline, Gallic Acid, Mangiferin and Quercetin) and a glucose metabolism regulatory target enzyme involved in type II diabetes, Glycogen Synthase Kinase 3 Beta (GSK3B) to assist potential antidiabetic drug search from natural source. ADME/T test assists in determining various physicochemical and pharmacological properties of lead molecules like their extent of adsorption inside the cell, extent of metabolism, solubility, blood brain barrier permeability, mutagenicity, carcinogenicity etc. which are the major prerequisites before marketing a drug. Quercetin performed well in overall experiment suggesting the best finding of the experiment. However, further in vitro/in vivo study is required to find out the best remedy of diabetes.

title: Oleanolic acid as a potential antidiabetic component of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) fruit: bioassay guided isolation and molecular docking studies
abstract: The present study was designed to conduct the bioassay guided isolation of possible bioactive compound(s) responsible for the antidiabetic action of Xylopia aethiopica (Dunal) A. Rich. fruit. The isolation of compound was guided by a glycosidase and a amylase inhibitory activities. Molecular docking with Autodock Vina was used to decipher the mode of interaction and binding affinity of the possible compound(s) with the selected enzymes. A pentacyclic triterpene, oleanolic acid (OA) was isolated from fruit and exhibited significantly (p 0.05) lower IC50 values (a amylase: 89.02 1.12 uM, a glucosidase: 46.05 0.25 uM) than other fractions and the acarbose. Interestingly, OA was found to bind to the a amylase and a glucosidase with minimum binding energy values of 0.9 and 1.2 kcal/mol respectively and none of the interactions involved hydrogen bond formation. Data of this study suggest that OA is responsible for the antidiabetic action of X. aethiopica fruit through the inhibition of a amylase and a glucosidase enzyme activities.

title: Antidiabetic, antioxidant, DFT and molecular docking studies of a triazene derivative and its transition metal complexes
abstract: A triazene derivative and its transition metal complexes were prepared and characterized using molar conductance, magnetic susceptibility measurements, IR, UV visible, NMR spectral studies wherever possible and applicable. The structure of the ligand and metal complexes was further confirmed using DFT calculations with the help of B97d method with 6 311++G(d,p) basis set. The antidiabetic and antioxidant activities of the ligand and the metal complexes were studied. The ligand showed potential biological activities which increased on chelation with metal ion. Apart from this, the molecular docking studies were carried out in order to understand the binding interaction of the ligand and its metal complexes with active sites of the target proteins.

title: Antidiabetic, antioxidant, molecular docking and HPTLC analysis of miquelianin isolated from Euphorbia schimperi C. Presl
abstract: The present study demonstrates the miquelianin or quercetin 3 O glucuronide (compound 1) isolated from aerial parts of Euphorbia schimperi exhibited significant results for antioxidant and antidiabetic potential. The compound 1 along with kaempferol 3 O glucuronide (compound 2) and quercetin 3 O rhamnoside (compound 3) isolated from the same source were quantified by validated HPTLC method. Antioxidant activity was determined by chemical means in terms of ABTS radical cation and DPPH radical scavenging activity. Compound 1 showed significant scavenging activity in both ABTS and DPPH assays as compared to standard BHA. In ABTS method IC50 values of compound 1 and standard BHA is found to be 58.90 3.40 ug/mL and 28.70 5.20 ug/mL respectively while in DPPH assay IC50 values of Compound 1 and standard BHA is 47.20 4.90 ug/mL and 34.50 6.20 ug/mL respectively. Antidiabetic effect was studied through a amylase and a glucosidase inhibitory activity. The mechanistic approach through molecular modelling also support the strong binding sites of compound 1 which showed significant a amylase and a glucosidase inhibitory activities with IC50 values 128.34 12.30 and 89.20 9.20 ug/mL respectively as compared to acarbose 64.20 5.60 and 52.40 4.60 ug/mL respectively. The results of validated RP HPTLC analyses revealed the concentration of compound 1 found to be 16.39 ug/mg and for compound 2 and compound 3 as 3.92 and 14.98 ug/mg of dried extract, respectively.

title: Benzoxazinone thiosemicarbazones as antidiabetic leads via aldose reductase inhibition: Synthesis, biological screening and molecular docking study.
abstract: Aldose reductase is an important enzyme in the polyol pathway, where glucose is converted to fructose, and sorbitol is released. Aldose reductase activity increases in diabetes as the glucose levels increase, resulting in increased sorbitol production. Sorbitol, being less cell permeable tends to accumulate in tissues such as eye lenses, peripheral nerves and glomerulus that are not insulin sensitive. This excessive build up of sorbitol is responsible for diabetes associated complications such as retinopathy and neuropathy. In continuation of our interest to design and discover potent inhibitors of aldo keto reductases (AKRs; aldehyde reductase ALR1 or AKR1A, and aldose reductase ALR2 or AKR1B) herein we designed and investigated a series of new benzoxazinone thiosemicarbazones (3a r) as ALR2 and ALR1 inhibitors. Most compounds exhibited excellent inhibitory activities with IC50 values in lower micro molar range. Compounds 3b and 3l were found to be most active ALR2 inhibitors with IC50 values of 0.52 0.04 and 0.19 0.03 mM, respectively, both compounds were more effective inhibitors as compared to the standard ALR2 inhibitor (sorbinil, with IC50 value of 3.14 0.02 mM)

title: Investigations on the structural, vibrational, computational, and molecular docking studies on potential antidiabetic chemical agent Diosmetin
abstract: In the present study, the harmonic vibrational frequencies of Diosmetin(5, 7 dihydroxy 2(3 hydroxy 4 methoxyphenyl) chromen 4 one) have been investigated by both experimental (FTIR and FT Raman) and theoretical (HF and DFT/B3LYP) method. The calculated harmonic vibrational frequencies were compared with experimental data. A detailed interpretation of the vibrational spectra of the compound has been made on the basis of the calculated potential energy distribution (PED) The 1H, 13C NMR chemical shifts and TD DFT calculations of the molecule were calculated and compared with the available experimental observations. A study on the molecular electrostatic potential surface (MEP) of the compound was performed, and the electrophilic and nucleophilic reactive sites were identified. Furthermore, the inhibition effect of compound against aldose reductase enzyme has been analyzed by molecular docking method, and the results were compared with the standard drug. The docking study indicates that the investigated compound shows better inhibitory activity toward aldose reductase enzyme than the standard drug, and hence this study may be supportive in the field of drug discovery to design more potential antidiabetic agents.