Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b] [1,4]benzothiazinium salts

A novel method of synthesizing 1,4-thiazine ring has led to the series of 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts. The derivatives containing a butyl or decyl substituents on the quinoline nitrogen atom were obtained by alkylation of 12(H)-quino[3,4-b][1,4]benzothiazine with alkyl bromides. Antiproliferative activity in vitro of the compounds (3) was assessed using two cancer cell lines (Hct116 and LLC) and doxorubicin as a reference. Most of the studied phenothiazine derivatives showed activity against both cell lines investigated (2.2–19.6 μg/mL concentration range). A structure–activity relationship was established. Only the compounds with substituents in the 11-position of the quinobenzothiazine ring did not exhibit activity against either cell line.

Graphical abstractA novel series of azaphenothiazine derivatives was synthesized. Antiproliferative activity of these 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts 3 was investigated in vitro using colorectal carcinoma (HCT116) and Lewis lung carcinoma (LLC) cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide