QSAR Modelling of Thymidylate Synthase Inhibitors in a Series of Quinazoline Derivatives

Thymidylate synthase (ThS) is a target for antimetabolite antitumor drugs. Such drugs have been used in the clinic although they cause several severe side effects and accumulate in tissues. Therefore, new less toxic ThS inhibitors must be sought and created. The GUSAR 2013 program was used to study...

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Bibliographic Details
Published in:Pharmaceutical chemistry journal 2018, Vol.51 (10), p.884-888
Main Authors: Khairullina, V. R., Gerchikov, A. Ya, Lagunin, A. A., Zarudii, F. S.
Format: Article
Language:English
Subjects:
Medicine
Organic Chemistry
Pharmacology/Toxicology
Pharmacy
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Summary:Thymidylate synthase (ThS) is a target for antimetabolite antitumor drugs. Such drugs have been used in the clinic although they cause several severe side effects and accumulate in tissues. Therefore, new less toxic ThS inhibitors must be sought and created. The GUSAR 2013 program was used to study the quantitative structure – activity relationship (QSAR) of a series of antifolate ThS inhibitors in the IC 50 range 0.52 – 24,800.00 nM. Statistically significant QSAR models were constructed using MNA- and QNA-descriptors and self-consistent regression. They typically predicted highly accurately the structures of the training and test sets ( R train 2 : 0.855 – 0.922; R train 3 : 0.810 – 0.895; R test 1 2 : 0.734 – 0.790; R test 2 2 : 0.800 – 0.835).
ISSN:0091-150X
1573-9031
DOI:10.1007/s11094-018-1710-z