title: New thiazacridine agents: Synthesis, physical and chemical characterization, and in vitro anticancer evaluation.
abstract: A series of new thiazacridine agents were synthesized and evaluated as antitumor agents, in terms of not only their cytotoxicity but also their selectivity. The cytotoxicity assay confirmed that all compounds showed cytotoxic activity and selectivity. The new compound, 3-acridin-9-ylmethyl-5-(5-bromo-1 H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/AA29 - 7a), proved to be the most promising compound as it presents lower half-maximal inhibitory concentration (IC50) values (ranging from 0.25 to 68.03 µM) depending on cell lineage. In HepG2 cells, the lowest IC50value was exhibited by 3-acridin-9-ylmethyl-5-(4-piperidin-1-yl-benzylidene)-thiazolidine-2,4-dione (LPSF/AA36 - 7b; 46.95 µM). None of the synthesized compounds showed cytotoxic activity against normal cells (IC50> 100 µM). The mechanism of death induction and cell cycle effects was also evaluated. Flow cytometric analysis revealed that the compounds LPSF/AA29 - 7a and LPSF/AA36 - 7b significantly increased the percentage of apoptotic cells and induced G2/M arrest in the cell cycle progression. Therefore, these new thiazacridine derivatives constitute promising antitumor agents whose cytotoxicity and selectivity properties indicate they have potential to contribute to or serve as a basis for the development of new cancer drugs in the future.
authors.affiliation: 1 Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Mbo
authors.initials: M
authors.lastname: Chagas
authors.affiliation: 2 Laboratory for Planning and Drug Synthesis, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Ncc
authors.initials: N
authors.lastname: Cordeiro
authors.affiliation: 1 Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Kmr
authors.initials: K
authors.lastname: Marques
authors.affiliation: 2 Laboratory for Planning and Drug Synthesis, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: M G
authors.initials: MG
authors.lastname: Rocha Pitta
authors.affiliation: 1 Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Mjbm
authors.initials: M
authors.lastname: Rêgo
authors.affiliation: 2 Laboratory for Planning and Drug Synthesis, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: McA
authors.initials: M
authors.lastname: Lima
authors.affiliation: 1 Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Mgr
authors.initials: M
authors.lastname: Pitta
authors.affiliation: 1 Laboratory for Immunomodulation and New Therapeutic Approaches, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.|2 Laboratory for Planning and Drug Synthesis, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: I R
authors.initials: IR
authors.lastname: Pitta
mesh_terms: D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D066244:Proton Magnetic Resonance Spectroscopy; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D045162:Thiazolidinediones
keywords: Acridine; anticancer activity; cell cycle; death induction mechanisms; thiazolidine