Quantitative Structure-Activity Relationship in the Series of 5-Ethyluridine, N2-Guanine, and 6-Oxopurine Derivatives with Pronounced Anti-Herpetic Activity.

Autor: Khairullina V; Institute of Chemistry and Defence in Emergency Situations, Ufa University of Science and Technology, 50076 Ufa, Russia., Martynova Y; Institute of Chemistry and Defence in Emergency Situations, Ufa University of Science and Technology, 50076 Ufa, Russia.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2023 Nov 22; Vol. 28 (23). Date of Electronic Publication: 2023 Nov 22.
DOI: 10.3390/molecules28237715
Abstrakt: A quantitative analysis of the relationship between the structure and inhibitory activity against the herpes simplex virus thymidine kinase (HSV-TK) was performed for the series of 5-ethyluridine, N2-guanine, and 6-oxopurines derivatives with pronounced anti-herpetic activity (IC 50 = 0.09 ÷ 160,000 μmol/L) using the GUSAR 2019 software. On the basis of the MNA and QNA descriptors and whole-molecule descriptors using the self-consistent regression, 12 statistically significant consensus models for predicting numerical pIC 50 values were constructed. These models demonstrated high predictive accuracy for the training and test sets. Molecular fragments of HSV-1 and HSV-2 TK inhibitors that enhance or diminish the anti-herpetic activity are considered. Virtual screening of the ChEMBL database using the developed QSAR models revealed 42 new effective HSV-1 and HSV-2 TK inhibitors. These compounds are promising for further research. The obtained data open up new opportunities for developing novel effective inhibitors of TK.
Databáze: MEDLINE
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