Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Medicinal chemistry research, 2014-11, Vol.23 (11), p.4956-4961

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2014

Quelle

SpringerLink

Beschreibungen/Notizen

• 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 5 H -pyrido[4,3- b ]carbazole-4,11(6 H )-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.