Synthesis and anticancer activity of bis-benzo[d][1,3]dioxol-5-yl thiourea derivatives with molecular docking study

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, IC50 values of 1,1'-(1,4-phenylene) bis(3-(benzo[d][1,3]dioxol-5-yl) thiourea) 5 were 2.38 mu M for HepG2, 1.54 mu M for HCT116 and 4.52 mu M for MCF7, while the IC50 values of standard drug doxorubicin were 7.46, 8.29 and 4.56 mu M, respectively. Interestingly, these compounds were non cytotoxic toward the tested normal cell line (IC50 value > 150 mu M). 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.