Design, synthesis and biological activity of DB02 amino acid derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors
10.16438/j.0513-4870.2022-0739
- VernacularTitle:非核苷类逆转录酶抑制剂DB02氨基酸衍生物的合成及抗HIV-1活性研究
- Author:
Jin-xuan YANG
1
,
2
;
Le YU
3
;
Yu-zhuo YANG
3
;
Rong-hua LUO
1
;
Yan-ping HE
3
;
Yong-tang ZHENG
1
Author Information
1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
2. College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
3. Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China
- Publication Type:Research Article
- Keywords:
DB02;
non-nucleoside reverse transcriptase inhibitor;
amino acid amide derivative;
anti-HIV-1 activity;
structure-activity relationship
- From:
Acta Pharmaceutica Sinica
2023;58(2):405-412
- CountryChina
- Language:Chinese
-
Abstract:
To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.
