Department of Chemistry, Faculty of Science, Taibah University, Almadinah Almunawarrah, Saudi Arabia.
Applied Organic Chemistry Department, National Research Centre, Cairo, Egypt; Faculty of Science and Arts, Mohail Asser, King Khalid University, Saudi Arabia.
Bioorg Chem. 2019 Sep;90:103088. doi: 10.1016/j.bioorg.2019.103088. Epub 2019 Jun 26.
New thiourea derivatives incorporating two benzo[d][1,3]dioxol-5-yl moieties have been synthesized through the reaction of two molecules of benzo[d][1,3]dioxol-5-yl isothiocyanate with one molecule of various diamino derivatives. The synthesized compounds were examined for their cytotoxic effects using SRB assay on three cancer cell lines HepG2, HCT116 and MCF-7. Most of compounds showed significant antitumor activity and some compounds showed strong results greater than the reference drug. As example, IC values of 1,1'-(1,4-phenylene)bis(3-(benzo[d][1,3]dioxol-5-yl)thiourea) 5 were 2.38 µM for HepG2, 1.54 µM for HCT116 and 4.52 µM for MCF7, while the IC values of standard drug doxorubicin were 7.46, 8.29 and 4.56 µM, respectively. Interestingly, these compounds were non cytotoxic toward the tested normal cell line (IC value > 150 µM). The anticancer mechanisms were studied via EGFR inhibition assessment, annexin V-FITC apoptosis assessment, cell cycle analysis and study the effect on mitochondrial apoptosis pathway proteins Bax and Bcl-2 as well as molecular docking studies.
已经通过两分子苯并[d][1,3]二恶唑-5-异硫氰酸酯与一分子各种二氨基衍生物的反应合成了包含两个苯并[d][1,3]二恶唑-5-基部分的新的硫脲衍生物。使用 SRB 测定法在三种癌细胞系 HepG2、HCT116 和 MCF-7 上测试了合成的化合物的细胞毒性作用。大多数化合物表现出显著的抗肿瘤活性，一些化合物表现出比参考药物更强的结果。例如，1,1'-(1,4-亚苯基)双(3-(苯并[d][1,3]二恶唑-5-基)硫脲)5 的 IC 值分别为 HepG2 为 2.38µM、HCT116 为 1.54µM 和 MCF7 为 4.52µM，而标准药物阿霉素的 IC 值分别为 7.46、8.29 和 4.56µM。有趣的是，这些化合物对测试的正常细胞系没有细胞毒性（IC 值>150µM）。通过 EGFR 抑制评估、Annexin V-FITC 凋亡评估、细胞周期分析以及研究对线粒体凋亡途径蛋白 Bax 和 Bcl-2 的影响以及分子对接研究研究了抗癌机制。
