CoMFA and CoMSIA studies on 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase inhibitors: Generation of homology model and docking studies

Aparoy, Polamarasetty; Suresh, G.; Reddy, Kakularam Kumar; Reddanna, Pallu

doi:10.1016/j.bmcl.2010.10.119

Cited by 21 publications

(5 citation statements)

References 28 publications

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“…Different statistics and methods can evaluate the predictive power of the model. For example, the external predictive correlation coefficients (r 2 pred values) [30,31,32] and four criteria proposed by Golbraikh [33]. Then, the statistics’ r 2 pred values were applied in this study, and the r 2 pred values are calculated using the following Equation (1): rpred2=1−PRESSSD…”

Section: Methodsmentioning

confidence: 99%

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

2016

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Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q 2 values (0.531, 0.726), fitted correlation r 2 coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

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Section: Methodsmentioning

confidence: 99%

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

2016

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“…To determine the key structural properties that affected the biological activities of the compounds under investigation, 3D-QSAR models were created using the CoMFA and CoMSIA techniques ( Aparoy et al, 2011 ; Tong et al, 2021 ). These techniques enabled examination of various molecular characteristics, such as electrostatic, steric, hydrogen-bond donor, hydrophobic, and hydrogen-bond acceptor, and their potential effects on biological activity ( Ouassaf et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

3D computer modeling of inhibitors targeting the MCF-7 breast cancer cell line

Zarougui,

Er-Rajy,

Faris

et al. 2024

Front. Chem.

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This study focused on developing new inhibitors for the MCF-7 cell line to contribute to our understanding of breast cancer biology and various experimental techniques. 3D QSAR modeling was used to design new tetrahydrobenzo[4, 5]thieno[2, 3-d]pyrimidine derivatives with good characteristics. Two robust 3D-QSAR models were developed, and their predictive capacities were confirmed through high correlations [CoMFA (Q2 = 0.62, R2 = 0.90) and CoMSIA (Q2 = 0.71, R2 = 0.88)] via external validations (R2ext = 0.90 and R2ext = 0.91, respectively). These successful evaluations confirm the potential of the models to provide reliable predictions. Six candidate inhibitors were discovered, and two new inhibitors were developed in silico using computational methods. The ADME-Tox properties and pharmacokinetic characteristics of the new derivatives were evaluated carefully. The interactions between the new tetrahydrobenzo[4, 5]thieno[2, 3-d]pyrimidine derivatives and the protein ERα (PDB code: 4XO6) were highlighted by molecular docking. Additionally, MM/GBSA calculations and molecular dynamics simulations provided interesting information on the binding stabilities between the complexes. The pharmaceutical characteristics, interactions with protein, and stabilities of the inhibitors were examined using various methods, including molecular docking and molecular dynamics simulations over 100 ns, binding free energy calculations, and ADME-Tox predictions, and compared with the FDA-approved drug capivasertib. The findings indicate that the inhibitors exhibit significant binding affinities, robust stabilities, and desirable pharmaceutical characteristics. These newly developed compounds, which act as inhibitors to mitigate breast cancer, therefore possess considerable potential as prospective drug candidates.

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“…To identify the most important structural properties governing the biological activity of the studied compounds, 3D-QSAR models were developed by adopting Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) techniques [ 23 , 24 ]. These techniques allow us to explore the effects of different molecular descriptors, including steric, electrostatic, hydrophobic, donor of hydrogen bonds and acceptor of hydrogen bonds, on biological activity [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Combined computational approaches for developing new anti-Alzheimer drug candidates: 3D-QSAR, molecular docking and molecular dynamics studies of liquiritigenin derivatives

Nour¹,

Daoui²,

Abchir³

et al. 2022

Heliyon

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CoMFA and CoMSIA studies on 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase inhibitors: Generation of homology model and docking studies

Cited by 21 publications

References 28 publications

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

3D computer modeling of inhibitors targeting the MCF-7 breast cancer cell line

Combined computational approaches for developing new anti-Alzheimer drug candidates: 3D-QSAR, molecular docking and molecular dynamics studies of liquiritigenin derivatives

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