Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents

Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents Научная публикация

Журнал

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Вых. Данные

Год: 2019, Том: 29, Номер: 23, Номер статьи : 126745, Страниц : DOI: 10.1016/j.bmcl.2019.126745

Ключевые слова

Antivirals; Camphor; Imine derivatives; Influenza; Camphecene

Авторы

Yarovaya Olga, I ^1,2 , Sokolova Anastasiya S. ¹ , Mainagashev Iliya Ya ¹ , Volobueva Alexandrina S. ³ , Lantseva Khristina ³ , Borisevich Sophia S. ⁴ , Shtro Anna A. ⁵ , Zarubaev Vladimir V. ³ , Salakhutdinov Nariman F. ^1,2

Организации

1	(Данные Web of science) Russian Acad Sci, NN Vorozhtsov Novosibirsk Inst Organ Chem, Siberian Branch, Lavrentjev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Pirogova St 2, Novosibirsk 630090, Russia
3	(Данные Web of science) Pasteur Inst Epidemiol & Microbiol, 14 Mira Str, St Petersburg 197101, Russia
4	(Данные Web of science) Russian Acad Sci, Ufa Fed Res Ctr, Ufa Inst Chem, Lab Chem Phys, 71 Octyabrya Pr, Ufa 450054, Russia
5	(Данные Web of science) Influenza Res Inst, Dept Chemotherapy, 15-17 Prof Popova St, St Petersburg 197376, Russia

A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC50 values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0-2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.

Yarovaya O.I. , Sokolova A.S. , Mainagashev I.Y. , Volobueva A.S. , Lantseva K. , Borisevich S.S. , Shtro A.A. , Zarubaev V.V. , Salakhutdinov N.F.
Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents
Bioorganic and Medicinal Chemistry Letters. 2019. V.29. N23. 126745 . DOI: 10.1016/j.bmcl.2019.126745 WOS Scopus РИНЦ

Опубликована в печати:

1 дек. 2019 г.

Web of science	WOS:000495112100022
Scopus	2-s2.0-85074404068
РИНЦ	41685891
OpenAlex	W2980781268