Synthesis and biological evaluation of novel 3,9-substituted β-carboline derivatives as anticancer agents

  • Bioorg Med Chem Lett. 2015 Sep 15;25(18):3873-7. doi: 10.1016/j.bmcl.2015.07.058.
Yi-Fong Chen  1 ,  Yi-Chien Lin  2 ,  Jeng-Pang Chen  2 ,  Hsu-Chin Chan  3 ,  Mei-Hua Hsu  2 ,  Hui-Yi Lin  2 ,  Sheng-Chu Kuo  1 ,  Li-Jiau Huang  4
Affiliations
  • 1. The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan, ROC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
  • 2. School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
  • 3. Department of Biochemistry, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
  • 4. The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan, ROC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC. Electronic address: [email protected].
PMID: 26235951 DOI: 10.1016/j.bmcl.2015.07.058
Abstract

In our previous studies on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesised numerous substituted carbazole and α-carboline derivatives, which exhibited Anticancer activity. In this study, we designed and synthesised a series of 3,9-substituted β-carbolines, by replacing the tricyclic rings of carbazole and α-carboline derivatives with isosteric β-carboline, and evaluated Anticancer activity. We observed that 9-(2-methoxybenzyl)-β-carboline-3-carboxylic acid (11a) inhibited the growth of HL-60 cells by inducing Apoptosis, with a half maximal inhibitory concentration of 4.0 μM. Our findings indicate that β-carboline derivatives can be used as lead compounds for developing novel antitumor agents.

Keywords
1-Benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs; Anticancer activity; Apoptosis; Structure–activity relationships (SARs); β-Carboline derivatives.