title: Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents.
abstract: Azaphenothiazines containing the quinoline ring, 8-10-substituted 6H-quinobenzothiazines and 6H-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.
authors.affiliation: a Department of Organic Chemistry , School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia , Sosnowiec , Katowice , Poland and.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jeleń
authors.affiliation: a Department of Organic Chemistry , School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia , Sosnowiec , Katowice , Poland and.
authors.forename: Krystian
authors.initials: K
authors.lastname: Pluta
authors.affiliation: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wrocław , Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
authors.affiliation: a Department of Organic Chemistry , School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia , Sosnowiec , Katowice , Poland and.
authors.forename: Beata
authors.initials: B
authors.lastname: Morak-Młodawska
authors.affiliation: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wrocław , Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Artym
authors.affiliation: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wrocław , Poland.
authors.forename: Maja
authors.initials: M
authors.lastname: Kocięba
authors.affiliation: b Department of Experimental Therapy , Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wrocław , Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kochanowska
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010293:Pargyline / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D013843:Thiazines; D010293:Pargyline
keywords: Anticancer activity; antiproliferative activity; apoptosis; azaphenothiazines; caspases