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Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells

Author(s):

Moacyr Jesus Barreto de Melo Rêgo, Wanessa Layssa Batista de Sena, Ricardo Olímpio de Moura, Iris Trindade Tenório Jacob, Thiago Ubiratan Lins e Lins, Michelly Cristiny Pereia, Maria do Carmo Alves de Lima, Marina Rocha Galdino-Pitta, Ivan da Rocha Pitta and Maira Galdino da Rocha Pitta   Pages 1 - 6 ( 6 )

Abstract:


Cancer has become one of the leading causes of morbidity and mortality worldwide. Limitations associated with existing agents increase the need to develop more effective anticancer drugs to improve the therapeutic arsenal available. Here, we describe the synthesis, characterization, toxicity and selectivity in vitro of three novel thiazacridine derivatives (ATZD): (Z)-5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-99), (Z)-5-acridin-9-ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-119) and (Z)-5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-129). In addition, changes in cell cycle and cell death induction mechanisms were assessed by flow cytometry. All compounds exhibited cytotoxicity to Raji (Burkitt’s lymphoma) and Jurkat (acute T cell leukemia) cells, where LPSF/AC-119 showed best IC50 values (0.6 and 1.53μM, respectively). LPSF/AC-129 was the only cytotoxic compound in glioblastoma cell line NG97 (IC50 = 55.77 μM). None of the compounds were toxic to normal human cells. All derivatives were more cytotoxic to hematopoietic neoplastic cells when compared to solid tumor cells. These compounds induced cell death primarily by apoptosis and are promising compounds for in vivo and combination therapy studies against cancer.

Keywords:

cancer; hematopoietic neoplastic cells; acridine; therapeutic innovation; cytotoxicity; apoptosis

Affiliation:

Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife, Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife, Biological Sciences Center, State University of Paraiba, Laboratory of Synthesis and Vectorization of Molecules, João Pessoa, Department of Antibiotics, Federal University of Pernambuco, Laboratory of Synthesis and Planning of Drug (LPSF), Recife, Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife, Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife, Department of Antibiotics, Federal University of Pernambuco, Laboratory of Synthesis and Planning of Drug (LPSF), Recife, Department of Antibiotics, Federal University of Pernambuco, Laboratory of Synthesis and Planning of Drug (LPSF), Recife, Department of Antibiotics, Federal University of Pernambuco, Laboratory of Synthesis and Planning of Drug (LPSF), Recife, Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife



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