Design, Synthesis, Anti-cancer Activities and Computational Analysis of Novel Diamides Conformationally Restricted by Cyclopropane

A series of diamides confonnationally restricted by cvclopropane were designed and synthesized. Most of the racemates containing cis-cyclopropane possessed promising inhibitory activity against four cancer cell lines (MCF-7, BGC-823, HepG2 and NCI-H460). In particular, racemate cis-N-1-(2-methyl-4-(perfluoropropan-2-yl)phenyl)-N-2-(4-phenoxy-benzyl)cyclopropane-1,2-dicarboxamide (1-19) showed the potential for further optimization as an anti-cancer lead with the IC50 value of (8.38 +/- 0.67) mg.L-1 on MCF-7. Moreover, sterol-sulfatase (STS) was predicated as the potential target protein and molecular docking was performed to explore the binding mode.