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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-11, Vol.27 (23), p.8115
• Main Authors: Vila, Noemí, Besada, Pedro, Brea, José, Loza, María Isabel, Terán, Carmen
• Format: Article
• Language: English
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; antiproliferative activity; Bromides; Cancer; Cancer therapies; Carbamates; Carbon disulfide; Cell Line, Tumor; Cell Proliferation; Chemical properties; Chlorine; dithiocarbamate; Drug Design; Drug development; Drug Screening Assays, Antitumor; drug-likeness; Female; Health aspects; Heterocyclic compounds; Humans; Hybridization; Hybrids; Kinases; Molecular Structure; one-pot synthesis; Ovarian cancer; Ovarian Neoplasms; Pharmaceutical research; Pharmacokinetics; phthalazinone; Selectivity; Structure-Activity Relationship; Toxicity; Tumor cell lines
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27238115

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 H PO , 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.