QSAR Modelling of Thymidylate Synthase Inhibitors in a Series of Quinazoline Derivatives
- Authors: Khairullina V.R.1, Gerchikov A.Y.1, Lagunin A.A.2,3, Zarudii F.S.4
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Affiliations:
- Department of Chemistry, Bashkir State University
- N. I. Pirogov Russian National Research Medical University
- V. N. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
- Bashkir State Medical University
- Issue: Vol 51, No 10 (2018)
- Pages: 884-888
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244842
- DOI: https://doi.org/10.1007/s11094-018-1710-z
- ID: 244842
Cite item
Abstract
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 IC50 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 (\( {\mathrm{R}}_{\mathrm{train}}^2 \): 0.855 – 0.922; \( {\mathrm{R}}_{\mathrm{train}}^3 \): 0.810 – 0.895;\( {\mathrm{R}}_{\mathrm{test}1}^2 \): 0.734 – 0.790; \( {\mathrm{R}}_{\mathrm{test}2}^2 \): 0.800 – 0.835).
About the authors
V. R. Khairullina
Department of Chemistry, Bashkir State University
Author for correspondence.
Email: Veronika1979@yandex.ru
Russian Federation, 32 Zaki Validi St., Ufa, Bashkortostan, 450076
A. Ya. Gerchikov
Department of Chemistry, Bashkir State University
Email: Veronika1979@yandex.ru
Russian Federation, 32 Zaki Validi St., Ufa, Bashkortostan, 450076
A. A. Lagunin
N. I. Pirogov Russian National Research Medical University; V. N. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
Email: Veronika1979@yandex.ru
Russian Federation, 1 Ostrovityanova St., Moscow, 117997; 10/8 Pogodinskaya St., Moscow, 119121
F. S. Zarudii
Bashkir State Medical University
Email: Veronika1979@yandex.ru
Russian Federation, 3 Lenina St., Ufa, Bashkortostan, 450077