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.

Spectroscopic and biological studies of a novel synthetic chlorin derivative with prospects for use in PDT.

Photosensitizers with desirable combinations of chemical, photophysical and biological properties are essential for improving the efficacy of photodynamic therapy (PDT) against various cancers. Chlorins seem to be promising candidates for photodynamic therapy (PDT) owing to their photophysical properties. This paper reports spectroscopic and biological properties of a novel synthetic chlorin derivative. Cytotoxicity, phototoxicity as well as subcellular localization of the novel derivative was studied using Lewis lung carcinoma cultured cells (LLC). In the examined concentration range no significant cytotoxic effects were found but high phototoxicity was observed. Confocal laser scanning microscopy demonstrated that the compound, upon entering cells, was localized in the perinuclear cytoplasm of LLC cells. Using fluorescent microscopy we investigated the impact of PDT based on the novel compound upon cytoskeleton and DNA structure of LLC cells. Our results indicate that liposomes are effective in transferring the chlorin photosensitizer into the studied cells, leading to their high photosensitization, whereas the non-carrier delivery mode (i.e., DMSO) is rather useless for such purposes.