Glycosylation derivatization, bioactivity evaluation of benzophenone polyphenols and their interaction with protein disulfide isomerase A6
10.16438/j.0513-4870.2023-1384
- VernacularTitle:二苯甲酮类多酚的糖基化衍生、活性评价及与PDIA6的相互作用
- Author:
Qiang LI
1
;
Ning-ning CHENG
1
;
Xiu-e FENG
2
;
Qing-shan LI
3
Author Information
1. School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China
2. School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China
3. School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong 030619, China
- Publication Type:Research Article
- Keywords:
benzophenone polyphenol;
synthesis;
glycosylation;
protein disulfide-isomerase A6;
anti-inflammation
- From:
Acta Pharmaceutica Sinica
2024;59(6):1706-1719
- CountryChina
- Language:Chinese
-
Abstract:
Protein disulfide isomerase A6 (PDIA6) is closely related to inflammation and endoplasmic reticulum stress. To obtain the glycosyl derivatives of benzophenone polyphenols targeting PDIA6 with strong anti-inflammatory effects, twenty-five target glycosyl derivatives were synthesized by Friedel-Crafts acylation and deacetylation reaction, starting from the substituted benzophenone and α-bromoacetyl saccharide, and their interactions with PDIA6 were quantitatively investigated by bio-layer interferometry (BLI) technique. Their in vitro anti-inflammatory properties were also evaluated. The results showed that target compounds 4b, 10b, 17b, 18b, and 25b not only exhibit high affinity with PDIA6, but also present strong anti-inflammatory abilities. Above results suggest that this class of compounds can affect the signaling pathways related to inflammation by directly acting on PDIA6. In particular, such compounds exhibit the strong inhibitory effects on IL-1β and IL-6 release, suggesting the potential development prospect in the treatment of inflammatory diseases.
