Andreani Aldo, Burnelli Silvia, Granaiola Massimiliano, Leoni Alberto, Locatelli Alessandra, Morigi Rita, Rambaldi Mirella, Varoli Lucilla, Calonghi Natalia, Cappadone Concettina, Voltattorni Manuela, Zini Maddalena, Stefanelli Claudio, Masotti Lanfranco, Shoemaker Robert H
Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
J Med Chem. 2008 Dec 11;51(23):7508-13. doi: 10.1021/jm800827q.
The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
报道了新型3-(5-咪唑并[2,1-b]噻唑基亚甲基)-2-吲哚酮和3-(5-咪唑并[2,1-b]噻二唑基亚甲基)-2-吲哚酮的合成。根据位于马里兰州贝塞斯达的美国国立癌症研究所（NCI）提供的方案评估了其抗肿瘤活性。为了研究该系列中最有效的抗肿瘤剂的作用机制，研究了其对HT-29结肠癌细胞生长的影响。其抑制细胞增殖的能力是通过细胞周期阻滞在G2/M期介导的，伴随着鸟氨酸脱羧酶（ODC）的抑制，鸟氨酸脱羧酶是多胺合成的限速酶，随后诱导细胞凋亡。
