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

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

Comb Chem High Throughput Screen. 2017 Jul 24;:

Authors: Jesus Barreto de Melo Rêgo M, Layssa Batista de Sena W, de Moura RO, Tenório Jacob IT, Lins E Lins TU, Pereia MC, Carmo Alves de Lima MD, Galdino-Pitta MR, Rocha Pitta ID, da Rocha Pitta MG

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.

PMID: 28738767 [PubMed - as supplied by publisher]

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