title: Synthesis and in vitro antiproliferative activity of novel 12(H)-quino[3,4-b][1,4]benzothiazine derivatives.
abstract: Novel method of N-dealkylating quinobenzothiazinium salts2,promoted by reaction with benzimidazole, led to a series of new azaphenothiazine derivatives having 12(H)-quino[3,4-b][1,4] benzothiazine4structure. Reaction of compounds4in an alkaline milieu with alkylating agents occur asN-alkylation of the thiazine nitrogen and yields quinobenzothiazine derivatives7. In vitro antiproliferative activity of compounds4and7was tested using two cancer cell lines (SNB-19 and C-32) and cisplatin as a reference. Most of the studied azaphenothiazine derivatives showed activity against both cell lines investigated (5.6-12.4 μg/ml concentration range tested). Compounds4(b-e) containing a halogen atom or methyl group at the 9-position of the quinobenzothiazine ring show activity in the tested concentration range only against C-32 cell line. Compound4fwith methyl group in 11-position of quinobenzothiazine ring lacked activity against either cell line. The presence of additional aminoalkyl substituents at the thiazine nitrogen atom in compounds7increases their activity against both examined cell lines, when compared to compounds4.
authors.affiliation: Department of Organic Chemistry, Medical University of Silesia, 41-200 Sosnowiec, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Zięba
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Latocha
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sochanik
keywords: Antiproliferative activity; Azaphenothiazine; Cisplatin; Phenothiazine; Quinobenzothiazine
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