title: Synthesis and anticancer activity of 2,4-disubstituted furo[3,2-b]indole derivatives.
abstract: We synthesized and evaluated a series of 2,4-disubstituted furo[3,2-b]indole derivatives for anticancer activity and established the structure-activity relationships (SARs) of these compounds. Among all tested compounds, we found (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl)furan-2-yl)methanol (10a) to be the most promising agent. In screening against NCI-60 human tumor cell lines, 10a exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cells. Our COMPARE analysis results suggest that the 10a fingerprint is similar to that of NSC-754549, which is an isostere of YC-1. We further confirmed the significant antitumor activity of compound 10a with tests in the A498 xenograft nude mice model. Therefore, compound 10a should be further developed as a new drug candidate for treating renal cancer.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan ROC.
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Zhuang
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lin
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chou
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hsu
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Huang
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles
keywords: A498 renal cancer cells; Anticancer activity; Furo[3,2-b]indole derivatives; Structure–activity relationships (SARs)