Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo
- Bioorg Med Chem. 2022 Apr 15:60:116705. doi: 10.1016/j.bmc.2022.116705.
- 1. School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, China.
- 2. College of Agronomy, Gansu Agricultural University, Lanzhou 730000, Gansu, China.
- 3. School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang Hunan 421001, China.
- 4. Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Xining 810008, China.
- 5. Tibetan Medical College, Qinghai University, Xining 810016, Qinghai, China; State Key Laboratory of Tibetan Medicine Research and Development, Xining 810016, Qinghai, China.
- 6. School of Pharmacy, Lanzhou University, Lanzhou 730000, Gansu, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang Hunan 421001, China. Electronic address: [email protected].
Isoquinoline alkaloid displays significant anti-gastric Cancer effects due to its unique structure, which is attracting more and more attention for the development of anti-gastric Cancer drugs. In this study, we explore the active components against gastric Cancer from the Tibetan Medicine Corydalis hendersonii Hemsl, which is rich in Isoquinoline Alkaloids. 14 compounds including 2 previously undescribed natural products were obtained. Interestingly, an new active compound displays potent anti-gastric Cancer activity. After accomplishing the total syntheses of the active compound and its derivatives, the anti-gastric Cancer activity of the active compound was further investigated. In vitro experiments revealed that the active compound significantly attenuated the proliferative capacity, caused G2/M phase arrest, inhibited the cell migration and invasion, and induced cell Apoptosis. Mechanistically, the active compound could increase the Bax/Bcl-2 ratio, elevate cytochrome c in the cytosol, and activate caspase-9/3, along with inactivating the upstream PI3K/Akt/mTOR signaling pathway. In addition, the active compound could also cause gastric Cancer cell death by inhibiting Topoisomerase I activity. More importantly, the anti-gastric Cancer activity of the active compound was confirmed in MGC-803 xenograft nude mice in vivo. This work not only promotes the exploitation of Corydalis hendersonii Hemsl., but also provides some experience for discovering new entities from natural sources.