Synthesis and antiproliferative activity of CBD aromatic ester derivatives

This study involved the synthesis of a series of novel cannabidiol (CBD) aromatic ester derivatives, including CBD-8,12-diaromaticester derivatives (compounds 2a-2t) and CBD-8,12-diacetyl-21-aromaticester derivatives (compound 5a-5c). The antiproliferative activities of these compounds against human liver cancer cell lines HePG2 and HeP3B as well as human pancreatic cancer cell lines ASPC-1 and BXPC-3 were evaluated in vitro using the CCK-8 assay. The results indicated that compound 2f exhibited an IC₅₀ value of 2.75 µM against HePG2, which is 5.32-fold higher than that of CBD. Additionally, compounds 2b and 5b demonstrated varying degrees of improved anticancer activity (IC₅₀ 5.95-9.21 µM) against HePG2.