Chalcogen bond-assisted syn-locked scaffolds: DFT analysis and biological implications of novel tubulin inhibitors.

A series of new tubulin inhibitors containing chalcogen bonds have been discovered. Density functional theory (DFT) analysis of the O-C-C-S torsion profile shows a preference of 0.8 kcal/mol for the syn-conformer over the anti-conformer. Besides, the O-S natural bond orbital (NBO) analysis reveals that the OLP âˆ¼ C-SBD∗ energy potential is 0.62 kcal/mol. Further pharmacochemical screening of several series of (4-arylthiophen-2-yl)(3,4,5-trimethoxyphenyl)methanones identified IPO-10 as a highly effective tubulin inhibitor with an IC50 of 23 nm for MCF-7.