QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP OF THE THYMIDYLATE SYNTHASE INHIBITORS OF MUS MUSCULUS IN THE SERIES OF QUINAZOLIN-4-ONE AND QUINAZOLIN-4-IMINE DERIVATIVES

KHAIRULLINA, V.R.; GERCHIKOV, A.Y.; MUSTAFIN, A.G.; GIMADIEVA, A.R.; ZARUDII, F.S.

QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP OF THE THYMIDYLATE SYNTHASE INHIBITORS OF MUS MUSCULUS IN THE SERIES OF QUINAZOLIN-4-ONE AND QUINAZOLIN-4-IMINE DERIVATIVES

KHAIRULLINA, V.R., GERCHIKOV, A.Y., MUSTAFIN, A.G., GIMADIEVA, A.R., ZARUDII, F.S.

Publication date: 2018

DOI: 10.1016/j.jmgm.2018.09.002

Abstract:

A quantitative structureeactivity relationship analysis of the 2-methylquinazolin-4-one and quinazolin-4-imine derivatives, well-known antifolate thymidylate synthase (TYMS) inhibitors, has been performedin the range IC50¼0.4÷380000.0 nmoL/L using the GUSAR 2013 program. Based on the MNA and QNAdescriptors using the self-consistent regression, 6 statistically significant consensus models for predictingthe IC50numerical values have been constructed. These models demonstrate high and moderate prog-nostic accuracies for the training and external validation test sets, respectively. The molecular fragmentsof TYMS inhibitors regulating their antitumor activity are identified. The obtained data open opportu-nities for developing novel promising inhibitors of TYMS.

Keywords:
Antifolate thymidylate synthase inhibitors, QSAR models, GUSAR 2013, QNA and MNA descriptors, Structureeactivity relationships, Scopus, Web of Science

Издатель: Elsevier Science Publishing Company, Inc.

Тип: Article

QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP OF THE THYMIDYLATE SYNTHASE INHIBITORS OF MUS MUSCULUS IN THE SERIES OF QUINAZOLIN-4-ONE AND QUINAZOLIN-4-IMINE DERIVATIVES

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