Synthesis and anti-proliferative activity of dehydroabietinol derivatives bearing a triazole moiety

Abstract

In search of more efficacious antitumor agents, a series of novel dehydroabietinol derivatives containing a triazole moiety was synthesized, and evaluated for cytotoxicity against four human cancer cell lines. Many exhibited superior cytotoxic profiles compared to the parent molecule, dehydroabietic acid. In particular, compounds 5g, 5i and 5j exhibited promising cytotoxicity with IC₅₀ values ranging from 4.84 to 9.62 μM against all the test cell lines. Cell clone formation and migration tests of compound 5g showed that it not only effectively inhibited the formation of MGC-803 cell colonies but also inhibited the MGC-803 cell migration and invasion. Additionally, the preliminary pharmacological mechanism indicated compound 5g induced apoptosis, arrested the mitotic process at the G0/G1 phase of the cell cycle, reduced the mitochondrial membrane potential, and increased the intracellular ROS and Ca²⁺ levels.