Application of 3D QSAR CoMFA/CoMSIA and in silico docking studies on novel renin inhibitors against cardiovascular diseases

Politi, A.; Durdağı, Serdar; Moutevelis‐Minakakis, Panagiota; Kokotos, George; Παπαδόπουλος, Μάνθος Γ.; Mavromoustakos, Thomas

doi:10.1016/j.ejmech.2009.03.040

Cited by 44 publications

(25 citation statements)

References 27 publications

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“…The Van Der Waals potentials and Coulombic terms were calculated by using Tripos force field. In CoMFA method a sp 3 hybridized carbon atom with a charge of 1e served as the probe atom to calculate steric and electrostatic fields, in which their energy values were truncated at 30 kcal/mol [12]. The CoMSIA method with the same lattice box that was used in CoMFA, incorporating steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor fields, were carried out using a probe atom with radius 1.0 Å , ?1.0 charge, and hydrophobic and hydrogen bond properties of ?1.…”

Section: Data Setsmentioning

confidence: 99%

3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

Lan

Xie

Yao

et al. 2010

J Comput Aided Mol Des

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Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave r (cv) (2) values of 0.614 and 0.598, r (2) values of 0.950 and 0.928, respectively. The external validation indicated that our CoMFA and CoMSIA models possessed high predictive powers with r (0) (2) values of 0.994 and 0.994, r (m) (2) values of 0.751 and 0.690, respectively. Molecular docking studies revealed that a phosphonic group was essential for binding to the receptor, and some key features were also identified. A set of forty new analogues were designed by utilizing the results revealed in the present study, and were predicted with significantly improved potencies in the developed models. The findings can be quite useful to aid the designing of new fructose-1,6-biphophatase inhibitors with improved biological response.

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Section: Data Setsmentioning

confidence: 99%

3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

Lan

Xie

Yao

et al. 2010

J Comput Aided Mol Des

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“…In CoMFA studies, a default sp 3 -carbon atom having a charge of ?1 and a van der Waals radius of 1.52 Å was used as a probe to calculate steric (Lennard-Jones 6-12 potential) field and electrostatic (Coulombic potential) field energies with a distance-dependent dielectric at each lattice point. The use of CoMFA and CoMSIA approaches together to provide better ability of visualization and interpretation of the obtained correlations in terms of field contributions (Politi et al, 2009). CoMSIA technique was also performed in our studies to obtain more information to design novel selective drugs.…”

Section: Molecular Structuresmentioning

confidence: 99%

“…PLS methodology is used to correlate AChE inhibitor activities with the CoMFA and CoMSIA values. A minimum column filtering value of 2.00 kcal mol/1 was set to improve the signal-to-noise ratio by omitting those grid points whose energy variation was below this threshold (Politi et al, 2009). The predictive value of the models was evaluated first by leave-one-out (LOO) cross-validation.…”

Section: Molecular Structuresmentioning

confidence: 99%

3D-QSAR study of multi-target-directed AchE inhibitors based on autodocking

et al. 2010

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We do some research about multi-targetdirected AChE inhibitors of Tacrine-Nimodipine dihydropyridine. 3D-QSAR models have been built using CoMFA and CoMSIA methods, based on compounds which are very selective and potent AChEIs and show an excellent neuroprotective profile and a moderate Ca 2? channel blockade effect. These studies indicated that the QSAR models were statistically significant and high predictable (receptor-based research CoMFA model, q 2 = 0.686, r 2 = 0.948; CoMSIA model, q 2 = 0.756, r 2 = 0.907 in all of the models no. of components = 6). Consequently, based on these results, our models would offer help to better comprehend the structure-activity relationships existent for this class of compounds and also facilitate the design of novel inhibitors with good chemical property.

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“…As an extension to the CoMFA approach, which has two fields, the CoMSIA method incorporates five different similar fields, namely steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor, were carried out using a probe atom with radius 1.0 Å , ?1.0 charge, and hydrophobic and hydrogen bond properties of ?1. The attenuation factor was set to the default value of 0.3 (Zhang and Zhong, 2010;Sun et al, 2010;Politi et al, 2009).…”

Section: Comfa and Comsia Setupmentioning

confidence: 99%

3D-QSAR studies on betulinic acid and betulin derivatives as anti-HIV-1 agents using CoMFA and CoMSIA

et al. 2010

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3D-QSAR studies were performed on a series of betulinic acid and betulin derivatives with anti-HIV-1 activities. 3D-QSAR models of analysis A and analysis B, which were related to two activity indexes EC 50 and TI, respectively, were built by using CoMFA and CoMSIA. The analysis A resulted from 41 molecules gave r cv 2 values of 0.664 and 0.718, r 2 values of 0.979 and 0.955, respectively. The analysis B also resulted from 41 molecules gave r cv 2 values of 0.570 and 0.559, r 2 values of 0.938 and 0.933, respectively. The contour maps generated from the two analyses provided the regions in space where interactive fields may influence the activity. The results could serve as a useful guide for the design of potential betulinic acid and betulin derivatives with better anti-HIV-1 activity.

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Application of 3D QSAR CoMFA/CoMSIA and in silico docking studies on novel renin inhibitors against cardiovascular diseases

Cited by 44 publications

References 27 publications

3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

3D-QSAR studies and molecular docking on [5-(4-amino-1H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

3D-QSAR study of multi-target-directed AchE inhibitors based on autodocking

3D-QSAR studies on betulinic acid and betulin derivatives as anti-HIV-1 agents using CoMFA and CoMSIA

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