QSAR and docking analysis of A2B adenosine receptor antagonists based on non-xanthine scaffold

Mansourian, Mahboubeh; Fassihi, Afshin; Saghaie, Lotfollah; Madadkar-Sobhani, Armin; Mahnam, Karim; Abbasi, Maryam

doi:10.1007/s00044-014-1133-7

Cited by 20 publications

(16 citation statements)

References 38 publications

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“…A QSAR model is exploited to screen new compounds when its domain of application has been defined [ 28 ]. The prediction may be assumed reliable for only those compounds which fall into this domain [ 29 ]. Standardized residuals of the activity were computed and were plotted versus leverage values (h).…”

Section: Resultsmentioning

confidence: 99%

“…The lower the value, the higher confidence in the prediction. Warning leverage (h*) is another standard for explanation of the results and is, generally, fixed at 3 (k + 1)/ n, where k is the number of model parameters and n is the number of calibration set [ 29 ]. Calculated leverage for calibration set is useful for determining the compounds which affect the model and, in terms of validation set, useful for assigning the applicability domain of the model.…”

Section: Resultsmentioning

confidence: 99%

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A study on quantitative structure–activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold

et al. 2015

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BackgroundMMP-2 enzyme is a kind of matrix metalloproteinases that digests the denatured collagens and gelatins. It is highly involved in the process of tumor invasion and has been considered as a promising target for cancer therapy. The structural requirements of an MMP-2 inhibitor are: (1) a functional group that binds the zinc ion, and (2) a functional group which interacts with the enzyme backbone and the side chains which undergo effective interactions with the enzyme subsites.MethodsIn the present study, a QSAR model was generated to screen new inhibitors of MMP-2 based on L–hydroxy tyrosine scaffold. Descriptors generation were done by Hyperchem 8, DRAGON and Gaussian98W programs. SPSS and MATLAB programs have been used for multiple linear regression (MLR) and genetic algorithm partial least squares (GA-PLS) analyses and for theoretical validation. Applicability domain of the model was performed to screen new compounds. The binding site potential of all inhibitors was verified by structure-based docking according to their binding energy and then the best inhibitors were selected.ResultsThe best QSAR models in MLR and GA-PLS were reported, with the square correlation coefficient for leave-one-out cross-validation (Q2LOO) larger than 0.921 and 0.900 respectively. The created MLR and GA-PLS models indicated the importance of molecular size, degree of branching, flexibility, shape, three-dimensional coordination of different atoms in a molecule in inhibitory activities against MMP-2.The docking study indicated that lipophilic and hydrogen bonding interactions among the inhibitors and the receptor are involved in a ligand-receptor interaction. The oxygen of carbonyl and sulfonyl groups is important for hydrogen bonds of ligand with Leu82 and Ala83. R2 and R3 substituents play a main role in hydrogen bonding interactions. R1 is sited in the hydrophobic pocket. Methylene group can help a ligand to be fitted in the lipophilic pocket, so two methylene groups are better than one. The Phenyl group can create a π-π interaction with Phe86.ConclusionsThe QSAR and docking analyses demonstrated to be helpful tools in the prediction of anti-cancer activities and a guide to the synthesis of new metalloproteinase inhibitors based on L-tyrosine scaffold.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A study on quantitative structure–activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold

et al. 2015

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“…The molecular structures were optimized using the Polak-Ribiere algorithm until the root mean square gradient was 0.01 kcal/mol/Å. Geometry optimization was run many times with different starting points of each 13 ligand ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, antimicrobial evaluation and docking studies of some novel quinazolinone Schiff base derivatives

Nasab¹,

Mansourian²,

Hassanzadeh³

2018

Res Pharma Sci

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The quinazolin-4(3H)-one structural motif possesses a wide spectrum of biological activities. DNA gyrase play an important role in induction of bacterial death. It has been shown that many quinazolin-4(3H)-one derivatives have antibacterial effects through inhibition of DNA gyrase. Based on this information we decided to synthesize novel quinazolinone Schiff base derivatives in order to evaluate their antibacterial effects. A series of novel quinazolinone Schiff base derivatives were designed and synthesized from benzoic acid. The potential DNA gyrase inhibitory activity of these compounds was investigated using in silico molecular docking simulation. All new synthesized derivatives were screened for their antimicrobial activities against three species of Gram-negative bacteria including Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis and three species of Gram-positive bacteria comprising of Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes as well as for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially against E. coli at 128 µg/mL concentration while no remarkable antifungal activities were observed for these compounds. All the synthesized compounds exhibit dock score values between -5.96 and -8.58 kcal/mol. The highest dock score among them was -8.58 kcal/mol for compound 4c.

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“…The crystal structure of the enzyme (PDB code 1KZN) with resolution 2.3 Å was chosen as the protein model for the current study. The structures of ligands were optimized using the HyperChem 7.0 software ( http://www.hyper.com ) as was explained previously ( 21 ). Auto Dock Tools were used to prepare the molecules and parameters before submitting it for docking analysis with Auto Dock ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…Lamarckian genetic algorithm (LGA) program with an adaptive whole method search in the Auto Dock was chosen to calculate the different ligand conformers ( 21 22 ). After 200 independent docking runs for each ligand, a cluster analysis was done.…”

Section: Methodsmentioning

confidence: 99%

Docking study, synthesis and antimicrobial evaluation of some novel 4-anilinoquinazoline derivatives

et al. 2017

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A series of novel 4-anilinoquinazoline derivatives were designed and synthesized from benzoic acid through ring closure, chlorination or nucleophilic substitution. The structures of compounds were characterized by IR, 1H-NMR and mass spectroscopy. All synthesized derivatives were screened for their antimicrobial activities against Gram-positive (Staphylococcus aurous, Bacillus subtilis, Listeria monocitogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) bacteria and also for antifungal activities against Candida albicans using the conventional micro dilution method. Most of the compounds have shown good antibacterial activities, especially compound 4c having highest activities against E. coli at 32 μg/mL concentration while the tested compounds did not exhibited remarkable antifungal activities. The potential DNA gyrase inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. All compounds showed good results especially compound 4c which showed the lowest ΔGbind results (-8.16 Kcal/mol).

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QSAR and docking analysis of A2B adenosine receptor antagonists based on non-xanthine scaffold

Cited by 20 publications

References 38 publications

A study on quantitative structure–activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold

A study on quantitative structure–activity relationship and molecular docking of metalloproteinase inhibitors based on L-tyrosine scaffold

Synthesis, antimicrobial evaluation and docking studies of some novel quinazolinone Schiff base derivatives

Docking study, synthesis and antimicrobial evaluation of some novel 4-anilinoquinazoline derivatives

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