Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures
10.16438/j.0513-4870.2023-1136
- VernacularTitle:不同母核结构苦豆碱衍生物合成及其抗冠状病毒活性研究
- Author:
Run-ze MENG
;
Yue GONG
;
Yu-long SHI
;
Kun WANG
;
Zong-gen PENG
;
Dan-qing SONG
- Publication Type:Research Article
- Keywords:
quaternary ammonium salt aloperine;
SARS-CoV-2;
ten-membered ring aloperine;
TMPRSS2;
SR-B1
- From:
Acta Pharmaceutica Sinica
2024;59(2):404-412
- CountryChina
- Language:Chinese
-
Abstract:
In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.
