Laboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil.
Molecules. 2013 Dec 6;18(12):15035-50. doi: 10.3390/molecules181215035.
Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 10(4) to 6.01 × 10(4) M(-1). UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.
噻嗪并吖啶和咪唑并吖啶衍生物在一些癌细胞系中作为肿瘤抑制剂显示出有希望的结果。为了更好地了解这些化合物的作用机制，通过电子吸收和荧光光谱以及圆二色性光谱研究了 5-吖啶-9-亚甲基-3-氨基-2-硫代-噻唑烷-4-酮、5-吖啶-9-亚甲基-2-硫代-噻唑烷-4-酮、5-吖啶-9-亚甲基-2-硫代-咪唑并[4,5-d]噻唑烷-4-酮和 3-吖啶-9-基甲基-噻唑烷-2,4-二酮与小牛胸腺 DNA（ctDNA）的结合。结合常数范围从 1.46×10(4)到 6.01×10(4)M(-1)。紫外-可见、荧光和圆二色性测量表明，这些化合物通过嵌入或外部结合有效地与 ctDNA 相互作用。除了 5-吖啶-9-亚甲基-2-硫代-1,3-噻唑烷-4-酮外，它们对人拓扑异构酶 I 都表现出抑制活性。这些结果为咪唑并吖啶和噻嗪并吖啶的 DNA 结合机制提供了深入的了解。
