title: Synthesis of 1,3-thiazine-2,4-diones with potential anticancer activity.
abstract: 2-Amino-1,3-thiazin-4-ones were subjected to acetylation followed by mild acid hydrolysis to give compounds containing the 1,3-thiazine-2,4-dione core. The potential of these S,N-containing heterocycles as antitumor agents against human cancer cell lines, among other types, was evaluated. The results show that phenyl- and naphthyl-substituted thiazinediones presented selective antitumoral activity against leukemia cells. These compounds caused cell death with DNA fragmentation and the mechanism of action seems to involve caspase cascade activation, imbalance in intracellular Ca(2+) and mitochondrial metabolism, and/or endoplasmic reticulum stress.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Misael
authors.initials: M
authors.lastname: Ferreira
authors.forename: Laura Sartori
authors.initials: LS
authors.lastname: Assunção
authors.forename: Fabíola Branco
authors.initials: FB
authors.lastname: Filippin-Monteiro
authors.forename: Tânia Beatriz
authors.initials: TB
authors.lastname: Creczynski-Pasa
authors.forename: Marcus Mandolesi
authors.initials: MM
authors.lastname: Sá
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D014227:Triazines; D002118:Calcium
keywords: 1,3-Thiazine-2,4-dione; Anticancer activity; Apoptosis; CVVMPGWDBRBKKE-XVNBXDOJSA-N; Leukemia; NKXNCVZOWAYPDG-VMPITWQZSA-N; OKKIUWDDFXXGEG-HAAWTFQLSA-N; PKPMKQQHKFLKTG-MDWZMJQESA-N; PPIPXCFJCUJOQW-VMPITWQZSA-N; RRFXLXBVXXOTNV-VCABWLAWSA-N; SEKDQSVUEANPDH-FPYGCLRLSA-N; UMMAVWCAWOSADO-RMKNXTFCSA-N