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

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.

Antitumor; SRSF1; Sulfur-substituted triptolide; Triptolide.