Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety As Potential Anticancer Agents

Nowadays, cancer disease seems to be the second most common cause of death worldwide. Molecular hybridization is a drug design strategy that has provided promising results against multifactorial diseases, including cancer. In this work, two series of phthalazinone-dithiocarbamate hybrids were described, compounds -, which display the dithiocarbamate scaffold at N2, and compounds , in which this moiety was placed at C4. The proposed compounds were successfully synthesized via the corresponding aminoalkyl phthalazinone derivatives and using a one-pot reaction with carbon disulfide, anhydrous HPO, and different benzyl or propargyl bromides. The antiproliferative effects of the titled compounds were explored against three human cancer cell lines (A2780, NCI-H460, and MCF-7). The preliminary results revealed significant differences in activity and selectivity depending on the dithiocarbamate moiety location. Thus, in general terms, compounds displayed better activity against the A-2780 and MCF-7 cell lines, while most of the analogues of the group were selective toward the NCI-H460 cell line. Compounds , , , -, , and with IC values less than 10 µM were the most promising. The drug-likeness and toxicity properties of the novel phthalazinone-dithiocarbamate hybrids were predicted using Swiss-ADME and ProTox web servers, respectively.