Synthesis and anticancer activity of 2,4,6-substituted furo[3,2-b]indole derivatives

• Main Authors: Shi-Hong Zhuang, 莊仕弘
• Other Authors: Li-Jiau Huang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/n6uzc2

博士 === 中國醫藥大學 === 藥物化學研究所博士班 === 102 === The purpose of this study is to develop compounds with potential anticancer activity as new anticancer drug candidate. A series of 2,4,6- substituted furo[3,2-b]indole derivatives were synthesized as target compounds and evaluated for in vitro anticancer activities against HL-60, Hep 3B, H460, A498, and Colo205 cancer cell lines. 4,6-Substituted-(furo[3,2-b]indol-2-yl)methanol (153, 155－163, 167－173, 175－180, 182－186, 188－211, 213 and 215) and 4,6-substituted- (thieno[3,2-b]indol-2-yl)methanol (154, 164－166, 174, 181, 187, 212, 214 and 216) were found with better anticancer activities. Among all the tested compounds, (5-((2-(hydroxymethyl)-furo[3,2-b]indol-4-yl) methyl)furan-2-yl) methanol (206) was found to be the most promising agent in the furo[3,2-b]indole derivatives, while (5-((2-(hydroxymethyl) -thieno[3,2-b]indol-4-yl)methyl)furan-2-yl) methanol (212) was found to be the most promising agent in the thieno[3,2-b]indole derivatives. When evaluated against NCI’s 60 human tumor cell line panel, compounds 206 and 212 exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cell. Furthermore, the result of COMPARE analysis suggested that the mode of action of 206 and 212 is very similar to YC-1. In addition, compound 206 exhibited significant anticancer activities when tested in a A498 xenograft nude mice model. Therefore, compounds 206 and 212 were identified as new lead compounds that merit further optimization.