Synthesis and antitumor evaluation of 5-(benzo[][1,3]dioxol-5-ylmethyl)-4-(-butyl)--arylthiazol-2-amines

• Published in: MedChemComm 2016-09, Vol.7 (9), p.1768-1774
• Main Authors: Wu, Z. L, Fang, Y. L, Tang, Y. T, Xiao, M. W, Ye, J, Li, G. X, Hu, A. X
• Format: Article
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c6md00234j

A series of novel N -aryl-5-(benzo[ d ][1,3]dioxol-5-ylmethyl)-4-( tert -butyl)thiazol-2-amines ( C1-C31 ) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC 50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC 50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC 50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC 50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent. The strategy for designing target compounds as antitumor agents.