Limits...
3D-QSAR studies on a series of dihydroorotate dehydrogenase inhibitors: analogues of the active metabolite of leflunomide.

Li SL, He MY, Du HG - Int J Mol Sci (2011)

Bottom Line: Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite.The statistical results, cross-validated r(CV) (2) (0.664) and non cross-validated r(2) (0.687), show a good predictive ability.The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.

View Article: PubMed Central - PubMed

Affiliation: College of Science, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing 100029, China; E-Mail: wulianhmy2008@163.com (M.-Y.H.).

ABSTRACT
The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated r(CV) (2) (0.664) and non cross-validated r(2) (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.

Show MeSH
Superposition of active analogues structures according to alignment 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3116169&req=5

f1-ijms-12-02982: Superposition of active analogues structures according to alignment 1.

Mentions: According to two alignment of the final active conformations of analogues, these compounds are then performed SOMFA analysis. The superposition of active analogues structures according to alignment 1 (considering phenyl ring similarity) has been shown in Figure 1, the superposition of active analogues according to the alignment 2 (considering all skeleton similarity) has also been shown in Figure 2. Using VEGA software [19], the final overlayed geometries are converted into CSSR file format, the only file format which the SOMFA2 program can accept to process a SOMFA analysis.


3D-QSAR studies on a series of dihydroorotate dehydrogenase inhibitors: analogues of the active metabolite of leflunomide.

Li SL, He MY, Du HG - Int J Mol Sci (2011)

Superposition of active analogues structures according to alignment 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3116169&req=5

f1-ijms-12-02982: Superposition of active analogues structures according to alignment 1.
Mentions: According to two alignment of the final active conformations of analogues, these compounds are then performed SOMFA analysis. The superposition of active analogues structures according to alignment 1 (considering phenyl ring similarity) has been shown in Figure 1, the superposition of active analogues according to the alignment 2 (considering all skeleton similarity) has also been shown in Figure 2. Using VEGA software [19], the final overlayed geometries are converted into CSSR file format, the only file format which the SOMFA2 program can accept to process a SOMFA analysis.

Bottom Line: Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite.The statistical results, cross-validated r(CV) (2) (0.664) and non cross-validated r(2) (0.687), show a good predictive ability.The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.

View Article: PubMed Central - PubMed

Affiliation: College of Science, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing 100029, China; E-Mail: wulianhmy2008@163.com (M.-Y.H.).

ABSTRACT
The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated r(CV) (2) (0.664) and non cross-validated r(2) (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme.

Show MeSH