В журнале European Journal of Medicinal Chemistry (IF=5.572) опубликована статья с участием сотрудников Института: к.х.н. А.С. Соколовой (снс, ЛФАВ), д.х.н.О.И. Яровой (внс, ЛФАВ), Е.Б. Мордвиновой (лаборантк, ЛФАВ), к.б.н. Д.С. Баева (снс, ЛФИ), д.б.н., проф. Т.Г. Толстиковой (завлаб ЛФИ) и чл.-корр. РАН, д.х.н., проф. Н. Ф. Салахутдинова (рук. отдела ОМХ, завлаб ЛФАВ)
Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process
Anastasiya S. Sokolova, Olga I.Yarovaya, Anastasiya V. Zybkina, Ekaterina D. Mordvinova, Nadezhda S. Shcherbakova, Anna V. Zaykovskaya, Dmitriy S. Baev, Tatyana G.Tolstikova, Dmitriy N. Shcherbakov, Oleg V .Pyankov, Rinat A. Maksyutov, Nariman F. Salakhutdinov
European Journal of Medicinal Chemistry
Available online 20 August 2020,
Volume 207, 1 December 2020, 112726
https://doi.org/10.1016/j.ejmech.2020.112726
Abstract
In this study, we screened a large library of (+)-camphor and (−)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC50 values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus. Compound 3b (As-358) exhibited the good antiviral potency (IC50 = 3.7 μM, SI = 118) against Marburg virus, while the hydrochloride salt of this compound 3b·HCl had a strong inhibitory effect against Ebola virus (IC50 = 9.1 μM, SI = 31) and good in vivo safety (LD50 > 1000 mg/kg). The results of molecular docking and in vitro mutagenesis analyses suggest that the synthesized compounds bind to the active binding site of EBOV glycoprotein similar to the known inhibitor toremifene.
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