Design and synthesis of novel sulfur-substituted triptolide with the ability to induce autophagy through inhibition of SRSF1 expression

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2025-02-02 DOI:10.1016/j.ejmech.2025.117342

Xinyi Chen , Jichen Guan , Yuzhi Lin, Haowen Luo, Junyi Liu, Jie Ma, Chuangjun Li, Dongming Zhang, Yingda Zang, Fangfang Lai

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Abstract

Six sulfur-substituted triptolide (TPL) analogs (STP1-6) were synthesized and evaluated for their biological functions. Among them, STP2 had significant antitumor activity both in vitro and in vivo. Notably, the intraperitoneal injections of 1 g/kg STP2 did not cause mice death and apparent pathological damage, while the mice in the TPL group (2 mg/kg) lost weight and all died within 4 days. The antitumor effect of STP2 could mediated by the inhibition of SRSF1 expression to regulate Bcl-x pre-mRNA splicing, which in turn induces autophagy and promotes cell death. This mechanism was the first time discovered in the field of TPL research. These results indicated that compound STP2 could be a promising lead compound for further studies.

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.