Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents. (3rd November 2016)

• Record Type: Journal Article
• Authors: Jeleń, Małgorzata; Pluta, Krystian; Zimecki, Michał; Morak-Młodawska, Beata; Artym, Jolanta; Kocięba, Maja; Kochanowska, Iwona
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31(2016:Jun.)Supplement 3
• Page Start: 83
• Page End: 88
• Publication Date: 2016-11-03
• Subjects: Anticancer activity -- antiproliferative activity -- apoptosis -- azaphenothiazines -- caspases; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2016.1205046
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Azaphenothiazines containing the quinoline ring, 8–10-substituted 6 H -quinobenzothiazines and 6 H -diquinothiazine were transformed into new 6-propargyl and 6-dialkylaminobutynyl derivatives containing the triple bond. Most of them displayed strong antiproliferative actions against human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin A (PHA), strongly suppressed lipopolysaccharide (LPS)-induced TNF-α production by whole blood human cell cultures, and exhibited low cytotoxicity. Three propargylquinobenzothiazines with the bromine, trifluoromethyl, and methylthio groups at position 9 and propargyldiquinothiazine exhibited comparable actions to cisplatin against the L-1210 and SW-948 tumor lines. 6-Propargyl-9-trifluoromethylquinobenzothiazine was shown to block caspase 3 expression and inhibit expression of caspase 8 and 9 in Jurkat cells indicating its possible mechanism of action. These derivatives could be promising, potential therapeutics for treatment of neoplastic diseases and autoimmune disorders.