3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

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 qua...

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Main Authors: Hong-Guang Du, Mao-Yu He, Shun-Lai Li
Format: Article
Language:English
Published: MDPI AG 2011-05-01
Series:International Journal of Molecular Sciences
Subjects:
DMARDs design
DHODH inhibitors
3D-QSAR
SOMFA
Online Access:http://www.mdpi.com/1422-0067/12/5/2982/
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spelling doaj-7d964057a459463f9c18d66055c3ee192020-11-25T00:26:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672011-05-011252982299310.3390/ijms120529823D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of LeflunomideHong-Guang DuMao-Yu HeShun-Lai LiThe 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 rCV2 (0.664) and non cross-validated r2 (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.http://www.mdpi.com/1422-0067/12/5/2982/DMARDs designDHODH inhibitors3D-QSARSOMFA
collection DOAJ
language English
format Article
sources DOAJ
author Hong-Guang Du
Mao-Yu He
Shun-Lai Li
spellingShingle Hong-Guang Du
Mao-Yu He
Shun-Lai Li
3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
International Journal of Molecular Sciences
DMARDs design
DHODH inhibitors
3D-QSAR
SOMFA
author_facet Hong-Guang Du
Mao-Yu He
Shun-Lai Li
author_sort Hong-Guang Du
title 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
title_short 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
title_full 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
title_fullStr 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
title_full_unstemmed 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide
title_sort 3d-qsar studies on a series of dihydroorotate dehydrogenase inhibitors: analogues of the active metabolite of leflunomide
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2011-05-01
description 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 rCV2 (0.664) and non cross-validated r2 (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.
topic DMARDs design
DHODH inhibitors
3D-QSAR
SOMFA
url http://www.mdpi.com/1422-0067/12/5/2982/
work_keys_str_mv AT hongguangdu 3dqsarstudiesonaseriesofdihydroorotatedehydrogenaseinhibitorsanaloguesoftheactivemetaboliteofleflunomide
AT maoyuhe 3dqsarstudiesonaseriesofdihydroorotatedehydrogenaseinhibitorsanaloguesoftheactivemetaboliteofleflunomide
AT shunlaili 3dqsarstudiesonaseriesofdihydroorotatedehydrogenaseinhibitorsanaloguesoftheactivemetaboliteofleflunomide
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