Concise synthesis and antiproliferative activity evaluation of ellipticine quinone and its analogs

Eur J Med Chem. 2017 Aug 18:136:1-13. doi: 10.1016/j.ejmech.2017.04.071.

Takashi Nishiyama ¹, Noriyuki Hatae ², Masataka Mizutani ³, Teruki Yoshimura ³, Tsuyoshi Kitamura ¹, Mana Miyano ¹, Mami Fujii ¹, Nanase Satsuki ¹, Minoru Ishikura ³, Satoshi Hibino ¹, Tominari Choshi ⁴

Affiliations

1 Graduate School of Pharmacy Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan.
2 Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. Electronic address: nhatae@hoku-iryo-u.ac.jp.
3 Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
4 Graduate School of Pharmacy Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan. Electronic address: choshi@fupharm.fukuyama-u.ac.jp.

PMID: 28477443 DOI: 10.1016/j.ejmech.2017.04.071

Abstract

We developed a concise protocol for the synthesis of ellipticine quinone from the appropriate 3-iodoindole-2-carbaldehydes in four steps. The key step is the construction of carbazole-1,4-quinone through tandem Ring-Closing Metathesis (RCM) and dehydrogenation under oxygen atmosphere. Therefore, the ellipticine quinone analogs possessing substitution at the 8- and/or 9-positions were synthesized using this method. In total, 14 compounds were evaluated for antiproliferative activity against HCT-116 and HL-60 cell lines; 9-nitroellipticine quinone was found to have superior activity compared to calothrixin B.

Keywords

Antiproliferative activity; Carbazole-1,4-quinone; Ellipticine quinone; Pyrido[4,3-b]carbozole-5,11-quinone; Ring-Closing Metathesis.

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