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