Title:Synthesis and Anticancer Evaluation of Thiazacridine Derivatives Reveals New Selective Molecules to Hematopoietic Neoplastic Cells
Volume: 20
Issue: 8
Author(s): Moacyr J.B. de Melo Rego*, Wanessa l.b. de Sena, Ricardo O. de Moura, Iris T.T. Jacob, Thiago U. Lins e Lins, Michelly C. Pereira, Maria do Carmo A. Lima, Marina R. Galdino-Pitta, Ivan da R. Pitta and Maira G. da Rocha Pitta
Affiliation:
- Department of Biochemistry, Federal University of Pernambuco, Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Recife,Brazil
Keywords:
Cancer, hematopoietic neoplastic cells, acridine, therapeutic innovation, cytotoxicity, apoptosis.
Abstract: Aim and Objective: 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. The aim of this study was to
synthesize and evaluate the antiproliferative effects of three new thiazacridine derivatives.
Material and Methods: Using a three steps synthesis reaction, three novel thiazacridine derivatives
were obtained and characterized: (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). Toxicity and selectivity assays were performed by colorimetric assay. Then,
changes in cell cycle and cell death induction mechanisms were assessed by flow cytometry.
Results: 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 1.53 µ M, respectively).
LPSF/AC-129 was the only cytotoxic compound in glioblastoma cell line NG97 (IC50 = 55.77 µ
M). None of the compounds were toxic to normal human cells and induced neoplastic cell death
primarily by apoptosis.
Conclusion: All derivatives were more cytotoxic to hematopoietic neoplastic cells when compared
to solid tumor derived cells. All three compounds are promising for in vivo and combination therapy
studies against cancer.
