Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents

Bioorg Med Chem. 2022 Jan 15:54:116581. doi: 10.1016/j.bmc.2021.116581.

Xiao-San Li ¹, Tang-Ji Chen ², Zhi-Peng Xu ³, Juan Long ², Miao-Ying He ², He-Hui Zhan ², Hai-Cai Zhuang ², Qi-Lin Wang ², Li Liu ⁴, Xue-Mei Yang ⁵, Jin-Shan Tang ⁶

Affiliations

1 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, PR China; Guangdong Zhanjiang Marine Biomedical Research Institute, Zhanjiang 524023, PR China.
2 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, PR China.
3 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
4 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, PR China. Electronic address: liuli-44@163.com.
5 Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, PR China. Electronic address: xuemeiyang131@163.com.
6 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China. Electronic address: gztangjinshan@126.com.

PMID: 34968813 DOI: 10.1016/j.bmc.2021.116581

Abstract

In order to study the structure-activity relationship (SAR) of C₂₁-steroidal glycosides toward human Cancer cell lines and explore more potential Anticancer agents, a series of 3β-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human Cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC₅₀ value of 3.11 μM. Mechanical studies showed that compound 2k induced both Apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve Anticancer activity for naturally occurring C₂₁-steroidal aglycones, and compound 2k represents a potential Anticancer agent deserved further investigation.

Keywords

3β-O-neoglycosides; Anticancer activity; Caudatin; Glycosylated modification.

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