Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor

SummaryNovel quinoline-dithiocarbamate hybrids were synthesized and designed by the molecular hybridization strategy. All these derivatives were evaluated for their antiproliferative activity against three selected cancer cell lines (MGC-803, HepG-2 and PC-3). Among them, compound10c displayed the best antiproliferative activity against PC-3 cells with an IC50 value of 0.43  μM. Celluar mechanisms investigated that compound10c could inhibit the migration against PC-3 cells by regulation the expression levels of E-cadherin and N-cadherin. Compound10c induced morphological changes of PC-3 cells and regulated apoptosis-related proteins (Bcl-2, Bax and Cleaved-Parp). In addition, compound10c inhibited tubulin polymerization in vitro with an IC50 value of 4.02  μM. Importantly, compound10c inhibited the growth of PC-3 cells in vivo with the low toxicity toward mice. These results suggested that compound10c might be an antitumor agent with potential for treating prostate cancer.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research