Medicinal Chemistry Research

, Volume 27, Issue 2, pp 412–419 | Cite as

Synthesis and cytotoxicity of pyrido[4,3-b]carbazole alkaloids against HCT-116 and HL-60 cells

  • Tomoki Itoh
  • Noriyuki Hatae
  • Takashi Nishiyama
  • Tominari Choshi
  • Satoshi Hibino
  • Teruki Yoshimura
  • Minoru Ishikura
Original Research


Ellipticine, olivacine, and their five reduced natural variants were synthesized via a palladium-catalyzed tandem cyclization/cross-coupling reaction as the key step. In addition, a previously unknown conformer of janetine was obtained through conformational inversion of the D ring in janetine. Because there are few synthetic approaches for reduced natural variants, little is known about the biological activities of these compounds. Six synthetic natural alkaloids and five of their derivatives were evaluated for their antiproliferative activity against HCT-116 and HL-60 cells. The activities of variants with the D-reduced ring or without the C(11)-Me group were lower than those of ellipticine. The conformer of guatambuine showed higher activities than guatambuine.


Pyrido[4,3-b]carbazole alkaloids Cytotoxicity HCT-116 cell HL-60 cell 



Half maximal inhibitory concentration


Thiazolyl blue tetrazolium bromide


Water-soluble tetrazolium salt-1



This study was supported in part by a Grant-in Aid for Scientific Research from the Japan Society for the Promotion of Sciences (No. 26460012 for M. I., and No. 17K08369 for N. H.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2068_MOESM1_ESM.pdf (7 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesHealth Sciences University of HokkaidoIshikari-TobetsuJapan
  2. 2.Graduate School of Pharmacy & Pharmaceutical Sciences, and Faculty of Pharmacy and Pharmaceutical SciencesFukuyama UniversityHiroshimaJapan

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