Lopes Marcela Silva, de Andrade Sena Camila Filizzola, Silva Bruno Leonardo, de Souza Cristina Maria, Ramos Jonas Pereira, Cassali Geovanni Dantas, de Souza-Fagundes Elaine Maria, Alves Ricardo Jose, de Oliveira Mônica Cristina, de Oliveira Renata Barbosa
Department of Pharmaceutical Products, Pharmacy Faculty, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Anticancer Agents Med Chem. 2015;15(2):206-16. doi: 10.2174/1871520614666141114201749.
Twenty-seven nitrated and non-nitrated compounds have been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines (IC50 < 8.5 μM). The cytotoxicity of the compounds on Vero cell line was established in vitro to evaluate the selectivity. All active compounds have a good leaving group (bromide or chloride) at the benzylic position, indicating that the mechanism of action of these compounds is related to their alkylating properties. Two compounds (3 and 24) were selected for further studies in mice with Ehrlich solid tumors and display significant antitumor effects in vivo.
已合成了27种硝化和非硝化化合物，并测试了它们对三种人类癌细胞系的生长抑制活性。14种化合物能够抑制至少一种癌细胞系50%以上的生长，5种化合物对人类癌细胞系表现出高抗增殖活性（IC50 < 8.5 μM）。在体外测定了这些化合物对Vero细胞系的细胞毒性，以评估其选择性。所有活性化合物在苄基位置都有一个良好的离去基团（溴或氯），这表明这些化合物的作用机制与其烷基化性质有关。选择了两种化合物（3号和24号）在患有艾氏实体瘤的小鼠中进行进一步研究，它们在体内显示出显著的抗肿瘤作用。
