scholarly journals Synthesis, Biological Activity and Molecular Docking of New Tricyclic Series as α-glucosidase Inhibitors

2018 ◽  
Author(s):  
Hatem A. Abuelizz ◽  
Nor Azman N. I Iwana ◽  
Rohaya Ahmad ◽  
Anouar El-Hassane ◽  
Mohamed Marzouk ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Digestive Enzymes ◽  
Postprandial Glucose ◽  
Glucose Absorption ◽  
Hydrogen Bond Interactions ◽  
Glucosidase Inhibitors ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Hydrolysis Of ◽  
Postprandial Glucose Level

AbstractDiabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 mM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand–α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.

scholarly journals Catalytic and Molecular Properties of Rabbit Liver Carboxylesterase Acting on 1,8-Cineole Derivatives

2012 ◽  
Vol 7 (9) ◽  
pp. 1934578X1200700
Author(s):  
María del H. Loandos ◽  
Ana C. Muro ◽  
Margarita B. Villecco ◽  
Marcelo F. Masman ◽  
Paul G.M. Luiten ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Molecular Modeling ◽  
Molecular Properties ◽  
Rabbit Liver ◽  
Enantioselective Hydrolysis ◽  
Docking Simulations ◽  
Hydrogen Bond Interactions ◽  
Molecular Dynamics Calculations ◽  
Hydrolysis Of

Rabbit liver carboxylesterase (rCE) was evaluated as the catalyst for the enantioselective hydrolysis of (±)-3-endo-acetyloxy-1,8-cineole [(±)-4], which yields (1S,3S,4R)-(+)-3-acetyloxy-1,8-cineole [(+)-4] and (1R,3R,4S)-(-)-3-hydroxy-1,8-cineole [(-)-3]. Enantioselective asymmetrization of meso-3,5-diacetoxy-1,8-cineol (5) gives (1S,3S,4R,5R)-(-)-3-acetyloxy-5-hydroxy-1,8-cineole (6), with high enantioselectivity. rCE has been chosen to perform both experiments and molecular modeling simulations. Docking simulations combined with molecular dynamics calculations were used to study rCE-catalyzed enantioselective hydrolysis of cineol derivatives. Both compounds were found to bind with their acetyl groups stabilized by hydrogen bond interactions between their oxygen atoms and Ser221.

Molecular modelling studies on thiazole-based α-Glucosidase Inhibitor using docking and CoMFA, CoMSIA and HQSAR

2020 ◽  
Vol 17 ◽  
Author(s):  
Deshbandhu Joshi ◽  
Shourya Yadav ◽  
Rajesh Sharma ◽  
Mitrunjaya Pandya ◽  
Raghvendra Singh Bhadauria
Keyword(s):  
Correlation Coefficient ◽  
Training Set ◽  
Glucosidase Inhibitors ◽  
Biological Dataset ◽  
Donor And Acceptor ◽  
Molecular Modelling Studies ◽  
Ic50 Values ◽  
Modelling Studies ◽  
Standard Error Estimation ◽  
Leave One Out

Aims and Objective: The biological dataset was retrieved from two series of α-glucosidase inhibitors synthesized by Rahim et al. and Taha et al. and consisted of a total 46 (forty-six) α-glucosidase inhibitors. Methods: The α-glucosidase inhibitory IC50 values (µM; performed against α-glucosidase from Saccharomyces cerevisiae) were converted into negative logarithmic units (pIC50). The CoMFA and CoMSIA models were created utilizing 37 as the training set and externally validated utilizing 9 as a test set. The CoMFA models MMFF94 were generated and ranging from 3.4661 to 5.2749 using leave-one-out PLS analysis cross-validated correlation coefficient q2 0.787 a high non-crossvalidated correlation coefficient r2 0.819 with a low standard error estimation (SEE) 0.041, F value 1316.074 and r2pred 0.996. Results: The steric and electrostatic fields contributions were 0.507 and 0.493, respectively. The CoMSIA model q2 0.805, r 2 0.833 was attained, (SEE) 0.065, F value 520.302 and r2pred 0.990. Contribution of steric, electrostatic, hydrophobic, donor and acceptor fields were 0.151, 0.268, 0.223, 0.234, 0.124 respectively. Conclusion: The HQSAR model of training set exhibits significant cross-validated correlation coefficient q2 0.800 and noncross-validated correlation coefficient r2 0.943.

Synthesis of Indolyl Pyrazole Scaffolds as Potential Anti-cancer Agents and their Molecular Modelling Studies

2020 ◽  
Vol 17 (7) ◽  
pp. 828-839
Author(s):  
Ganga Reddy Gaddam ◽  
Pramod Kumar Dubey ◽  
Venkata Ramana Reddy Chittireddy
Keyword(s):  
Cell Lines ◽  
Biological Activities ◽  
Moderate Activity ◽  
Lung Cancer Cell ◽  
Anti Cancer ◽  
A549 Lung Cancer Cell ◽  
New Chemical Entities ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
A549 Lung

Background:: Indole and pyrazoles are one of the prime structural units in the field of medicinal chemistry and have been reported to exhibit a variety of biological activities specifically anti-cancer. In view of their medicinal significance, we synthesized a conjugate of the two moieties to get access to newer and potential anti-cancer agents. Methods: Indolyl pyrazoles [3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-indole-3-carbon yl)acrylonitriles] (4a-l) were synthesized by adopting simple and greener protocol and all the synthesized derivatives were docked against Bcl-2 protein and the selected chemical moieties were screened for their cytotoxicity by using the MTT assay. Results: : All the synthesized compounds were docked against BCL-2 protein in order to understand their binding pattern. Among the 12 compounds docked, 4d, 4f, 4h, 4j, and 4l compounds exhibited better protein binding interactions and the same were screened for their anti-cancer activity against A549 (lung) cancer cell lines at a concentration of 100 μM using Doxorubicin as standard. Substitutions such as N-benzyl, N-ethyl groups and halogen groups such as Br, Cl on indole ring showed moderate activity against A-549 cell lines. Conclusion:: Among the 5 indolyl pyrazole derivatives screened, compounds 4h and 4j showed significantly better activity with an IC50 of 33.12 and 34.24 μM, respectively. Further, structural tweaking of the synthesized new chemical entities may lead to potential hit/lead-like molecules.

Stereospecific Association of C-20 Epimers of 3β-Hydroxy-16-oxo-24-nor-17-azachol-5-eno-23-nitryle

1997 ◽  
Vol 52 (6) ◽  
pp. 749-756
Author(s):  
Zofia Plesnar ◽  
Stanisław Malanowski ◽  
Zenon Lotowski ◽  
Jacek W. Morzycki ◽  
Jadwiga Frelek ◽  
...  
Keyword(s):  
Proton Nuclear Magnetic Resonance ◽  
Side Chain ◽  
Water Molecules ◽  
Carbonyl Groups ◽  
Nmr Data ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Lactam Carbonyl ◽  
Self Association ◽  
Chain Conformations

Abstract The cryoscopic measurements show that title compounds are strongly associated in CHCl3 solutions. The association of the 20 R epimer is distinctly less pronounced than that of the 20 S epipmer. Self-association of the 20 S epimer leads to the formation of very large com­plexes. The 20 R epimer forms associates via water molecules. The dissimilarity may be ex­plained in terms of different accessibility of the lactam carbonyl groups in the two epimers for the association. It is proposed that the association process is controlled by the configura­tion at the carbon atom C(20) and conformation around the C(20)-C(22) bond. Populations of side chain conformations of both epimers were determined by means of proton nuclear magnetic resonance. It was found for the 20 R epimer that the t and the -g rotamers are almost equally populated, and the rotamer +g is excluded. For the 20 S epimer the +g rotamer predominates over the t one, and the -g rotamer is excluded. The NMR data are fully consistent with the results of the molecular modelling studies.

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