Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles
作者:Wiliam Caneschi、Karine Braga Enes、Camille Carvalho de Mendonça、Fábio de Souza Fernandes、Fabio Balbino Miguel、Jefferson da Silva Martins、Mireille Le Hyaric、Roberto Rosas Pinho、Lucas Mattos Duarte、Marcone Augusto Leal de Oliveira、Hélio F. Dos Santos、Miriam Teresa Paz Lopes、Dalton Dittz、Heveline Silva、Mara Rubia Costa Couri
DOI:10.1016/j.ejmech.2019.01.001
日期:2019.3
A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro
合成了一系列1,2,4-和1,3,4-恶二唑衍生物,并评估了其抗癌活性。卤代的1,2,4-恶二唑从苄腈获得,并与亲脂性胺或氨基醇偶联。亲脂性1,3,4-恶二唑衍生物是通过5-(芳基)-1,3,4-恶二唑-2-硫醇与烷基化或酰化胺之间的曼尼希反应获得的。在体外的细胞毒性效应对4T1-乳腺癌评价和CT26 -结肠癌细胞。1,3,4-恶二唑与具有10-14个碳链部分的烷基化哌嗪偶联的IC 50为最佳 对于4T1细胞系,其值范围为1.6至3.55μM,对于CT26.WT细胞系,其值范围为1.6至3.9μM,选择性指数最高为19。最有效的化合物采用AnnexinV和PI染色进行了研究,可作为细胞凋亡诱导的指示。