Structure-activity relationships of novel dithiocarbamates containing α,β-unsaturated ketone fragment as potent anticancer agents

AbstractBased on the structure of novel lead compound8 discovered by our group, systematic structural modification was carried out. A series of compound8’s derivatives were synthesized and evaluated for their activities against human non-small cell lung cancer cell line H460. Among them, twelve compounds showed significant proliferation inhibition activities with IC50 values<1  μM and compound12r was the most potent one. Further study on compound12r revealed that it has significant inhibitory effect on the growth of eight kinds of cancer cell lines with IC50 values<1  μM. Especially for cell lines A375 and HCT116, the IC50 values of12r achieved 63  nM and 66 nM, respectively. Meanwhile, our research results also revealed the following structure-activity relationships: (a) different substitutions on the benzene ring or heteroaromatic rings greatly effect on the activity; (b) the presence of α,β-unsaturated ketone fragment is favorable fo r the activity; (c) the receptor cavity binding with amine moiety might be a relatively small hydrophobic cavity. These results will be valuable for the further development of this novel kind of dithiocarbamates.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research