title: Exploring stereoselectivity of 3-indolyl cyclopent[b]indoles: a parallel synthesis and anti-EGFR study on human cancer cells.
abstract: We synthesized a series of novel 3-indolyl cyclopent[b]indoles by trifluoroacetic acid mediated cyclodimerizations. The reaction showed high stereoselectivity and moderate to good yields. The influencing factors for stereoselectivity were systematically analyzed and a stepwise reaction mechanism was proposed. The cell viability tests in two colon and two lung cancer cell lines indicated the 1-benzyl-2-phenyl-group in 3-indolyl cyclopent[b]indoles was critical for the observed lower IC₅₀s in these compounds. Western blot analysis demonstrated that the compound inhibited the expression and phosphorylation of EGFR through altered HSP90 expression. Further cell cycle and cell cycle check point protein analyses showed expected anti-cellular proliferation and cell cycle arresting properties associated with suppressed EGFR expression and phosphorylation. These data revealed a novel molecular mechanism explaining the observed cytotoxicities for these compounds.
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Dacheng
authors: D
authors: Fan
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; National Institute of Health Care Products for Animals, Qingdao Continent Pharmaceuticals Co., Ltd., Qingdao 266111, Shandong, China.
authors: Weizhi
authors: W
authors: Sun
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Peiju
authors: P
authors: Qiu
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Zhiyong
authors: Z
authors: Wu
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Yantuan
authors: Y
authors: Li
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
authors: Shengbiao
authors: S
authors: Wan
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. Electronic address: jiangtao@ouc.edu.cn.
authors: Tao
authors: T
authors: Jiang
authors: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China. Electronic address: lijuanzhang@ouc.edu.cn.
authors: Lijuan
authors: L
authors: Zhang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D010766:Phosphorylation; D013237:Stereoisomerism
chemical_list: D007211:Indoles; D066246:ErbB Receptors
keywords: 3-Indolyl cyclopent[b]indole; Cell cycle; Cyclodimerization; EGFR; Lewis acid; Stereoselective