2. Academic Validation
  3. Discovery of α-carboline fused benzofuran-containing anticancer agents as rapid apoptosis inducers through intrinsic pathway

Discovery of α-carboline fused benzofuran-containing anticancer agents as rapid apoptosis inducers through intrinsic pathway

  • Eur J Med Chem. 2026 Feb 5:303:118464. doi: 10.1016/j.ejmech.2025.118464.
Fang Lin 1,  Zhangshun Luo 1,  Qinyu Wu 1,  Lijie Lv 1,  Zhonghong Chen 1,  Yi He 1,  Hai-Xin Yuan 2,  Yahui Zhao 3,  Shenyou Nie 4
Affiliations

Affiliations

  • 1 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Department of Urology and Department of Cancer Center of the Second Affiliated Hospital & College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China. Electronic address: yuanhaixin@cqmu.edu.cn.
  • 3 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China. Electronic address: zhaoyahui@cqmu.edu.cn.
  • 4 Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Department of Urology and Department of Cancer Center of the Second Affiliated Hospital & College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China. Electronic address: nieshenyou@cqmu.edu.cn.
PMID: 41365087 DOI: 10.1016/j.ejmech.2025.118464
Abstract

Apoptosis, a programmed form of cell death, typically requires several hours to initiate cytochrome c release following stimuli. Facilitating Apoptosis plays a decisive role in eliminating detrimental cells as well as in Cancer treatment. In this study, diverse novel α-carboline-fused benzofuran collections were efficiently achieved via C-H activation/Lossen rearrangement/[4 + 2] cyclization cascades. Among them, compound 10 was found to rapidly induce Apoptosis through the intrinsic pathway by releasing cytochrome c within 10 min, followed by cleavage and activation of caspase-9, Caspase-3, and PARP1. Mechanistically, compound 10 was found to potently inhibit several signaling cascades that are important for cell proliferation and survival, including Akt, ERK1/2, STAT1, STAT3, and S6K, suggesting its role as a multi-kinase inhibitor in inducing rapid Apoptosis. Furthermore, compound 10 significantly inhibited tumor growth in a mouse xenograft model. Overall, this novel inducer of rapid Apoptosis may serve as a powerful tool for further elucidation of apoptotic mechanisms and holds promising therapeutic potential in clinical Cancer treatment.

Keywords

Anticancer; Apoptosis inducer; Benzofuran; Multi-kinase inhibitor; α-carboline.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z