Design and synthesis of novel N()-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents.

A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.