title: Design, synthesis and antiproliferative activity of a novel class of indole-2-carboxylate derivatives.
abstract: Based on the chemical structure of Pyrroloquinoline quinone (PQQ), a novel class of indole-2-carboxylate derivatives was designed, synthesized and assayed for antiproliferative activity in cancer cells in vitro. The biological results showed that some derivatives exhibited significant antiproliferative activity against HepG2, A549 and MCF7 cells. Notably, the novel compounds, methyl 6-amino-4-cyclohexylmethoxy-1H-indole-2-carboxylate (6e) and methyl 4-isopropoxy-6-methoxy-1H-indole-2-carboxylate (9l) exhibited more potent antiproliferative activity than the reference drugs PQQ and etoposide in vitro, with IC50 values ranging from 3.78 ± 0.58 to 24.08 ± 1.76 μM. Further biological assay showed that both compounds 6e and 9l increased ROS generation dose-dependently, and induced PARP cleavage in A549 cells. Consequently, 6e and 9l appeared as promising anticancer lead compounds for further optimization.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Xing-yue
authors.initials: XY
authors.lastname: Ji
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Si-tu
authors.initials: ST
authors.lastname: Xue
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yue-chen
authors.initials: YC
authors.lastname: Zhan
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jia-jia
authors.initials: JJ
authors.lastname: Shen
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Lin-tao
authors.initials: LT
authors.lastname: Wu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: wangzhen@imb.pumc.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: lizhuorong@imb.pumc.edu.cn.
authors.forename: Zhuo-rong
authors.initials: ZR
authors.lastname: Li
mesh_terms: 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; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D017382:Reactive Oxygen Species; C503382:indole-2-carboxylate; D011065:Poly(ADP-ribose) Polymerases
keywords: Antiproliferative activities; Indole-2-carboxylate derivatives; PQQ; ROS generation