N-Substituted calothrixin B derivatives inhibited the proliferation of HL-60 promyelocytic leukemia cells

Noriyuki Hatae, Risa Satoh, Hitomi Chiba, Takahiro Osaki, Takashi Nishiyama, Minoru Ishikura, Takumi Abe, Satoshi Hibino, Tominari Choshi, Chiaki Okada, Eiko Toyota

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Calothrixin B, whose structure consists of a pentacyclic indolo[3,2-j]phenanthridine framework, was originally isolated as a secondary metabolite from Calothrix cyanobacteria and was found to exhibit potent antiproliferative activity. In this study, treatment with 100 μM of calothrixin B did not inhibit the proliferation of HL-60 promyelocytic leukemia cells, the result indicated that calothrixin B could possess weaker activity against leukemia cells. In a previous study of the structure-antiproliferative activity relationships of calothrixin B analogs, the tetracyclic 5H-pyrido[4,3-b]carbazole-4,11(6H)-dione structure, which does not include the benzene ring found in calothrixin B, was reported to be necessary for antiproliferative activity; however, the induction of substituents on the indole nitrogen atom of calothrixin B decreased the antiproliferative activity of the compound. To develop calothrixin B analogs with good antiproliferative activity against both HL-60 and HCT-116 cells, we synthesized various N-substituted calothrixin B analogs and assessed their activity. Compared with calothrixin B, N-OMe calothrixin B displayed almost the same or slightly stronger antiproliferative activity against HCT-116 cells, whereas the N-MOM analog demonstrated slightly weaker activity against these cells. These two analogs also inhibited proliferation of HL-60 cells, whereas calothrixin B did not exhibit antiproliferative activity toward these cells. Among calothrixin B analogs, N-OMe and N-MOM calothrixins B are cytotoxic against HCT-116 cells and not the lack of the effect on HL-60 cells.

Original languageEnglish
Pages (from-to)4956-4961
Number of pages6
JournalMedicinal Chemistry Research
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 2014
Externally publishedYes

Keywords

  • Antiproliferative activity
  • Calothrix cyanobacteria
  • Calothrixin B
  • HL-60 cells
  • N-OMe calothrixin B

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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