Synthesis and In Silico Prediction of the Molecular-Targeting Anti-EGFR Action of a Novel Dihydroacridinone

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发表日期：

2024年3月1日

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A. A. Epishkina,
E. V. Bogoslovskaya,
V. A. Pakina,
A. I. Osipiantz,
E. A. Kutorkina,
E. A. Livin,
O. M. Tumutolova,
S. Ya. Skachilova,
K. D. Blinov,
E. V. Semeleva,
D. N. Shimanovsky,
I. V. Fedoseikin,
M. V. Tolstov,
E. V. Blinova,
E. V. Shikh,
D. S. Blinov

摘要

The synthesis and in silico prediction of the molecular-targeted anti-EGFR inhibitory activity of a novel dihydroacridinone derivative are reported. 9-Aminium-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one L-2-hydroxybutanedioate (LHT-17-19) was obtained 99.8% pure by mixing and heating equimolar amounts of 9-amino-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one and L-2-hydroxybutanedioic acid in 50% EtOH. Virtual molecular screening of the spectrum of effects of the compound revealed inhibitory properties against several intracellular targets, i.e., carcinogenesis drivers, among which the EGFR kinase domain had the highest probability. Docking of LHT-17-19 base to the EGFR kinase domain formed a molecular complex with a high affinity and bonding energy. The results suggested that LHT-17-19 had high antitumor activity against malignant neoplasms expressing EGFR.