A series of novel thiazolo[3,2-b][1,2,4]-triazoles 3a-n has been synthesized and evaluated in vitro as potential antiproliferative. Compounds 3b-d exhibited significant antiproliferative activity. Compound 3b was the most potent with Mean GI₅₀ 1.37 µM comparing to doxorubicin (GI₅₀ 1.13 µM). The transcription effects of 3b, 3c and 3d on the p53 were assessed and compared with the reference doxorubicin. The results revealed an increase of 15–27 in p53 level compared to the test cells and that p53 protein level of 3b, 3c and 3d was significantly inductive (1419, 571 and 787 pg/mL, respectively) in relation to doxorubicin (1263 pg/mL). The docking study of the new compounds 3a-n revealed high binding scores for the new compounds toward p53 binding domain in MDM2. The docking analyses revealed the highest affinities for compounds 3b-d which induced p53 activity in MCF-7 cancer cells. Compound 3b which exhibited the highest antiproliferative activity and induced the highest increase in p53 level in MCF-7 cells showed also the highest affinity to MDM2.

合成了一系列新型的噻唑并[3,2- b ] [1,2,4]-三唑3a-n，并在体外评价为潜在的抗增殖剂。化合物3b-d显示出显着的抗增殖活性。与阿霉素（GI ₅₀ 1.13 µM）相比，化合物3b的平均GI ₅₀ 1.37 µM最有效。评估了3b，3c和3d对p53的转录作用，并与参考阿霉素进行了比较。结果显示与测试细胞相比，p53水平提高了15–27，p53蛋白水平分别为3b，3c和3d相对于阿霉素（1263 pg / mL）具有显着诱导性（分别为1419、571和787 pg / mL）。新化合物3a - n的对接研究表明，新化合物对MDM2中p53结合域的结合得分很高。对接分析揭示了在MCF-7癌细胞中诱导p53活性的化合物3b-d的最高亲和力。在MCF-7细胞中表现出最高抗增殖活性并诱导最高p53水平升高的化合物3b也显示出对MDM2最高的亲和力。