Semi-Synthesis and Evaluation of Cannabichromene-Derived Amine and Amide Analogues as Anticancer Agents

Abstract A novel series of cannabichromene-derived amine and amide analogues (4−13) was synthesized and evaluated for their anticancer activity against the NCI-60 human tumor cell line panel. Among the synthesized derivatives, compounds 8 and 9 demonstrated the most potent and broad-spectrum anticancer activities, exhibiting significant percent growth inhibition across multiple cancer subtypes. Notably, compound 9 displayed good potency in prostate cancer cell lines PC-3 and DU-145, with GI50 values of 2.01 μM and 1.86 μM, respectively and pronounced cytotoxicity at higher concentrations. Its consistent performance across diverse cancer panels suggests a non-selective yet potent mechanism, likely targeting essential cellular pathways common to malignant cells. Compound 9 was found to induce apoptosis in PC-3 and DU-145 cells. Collectively, these findings highlight 9 as a promising compound for further optimization and mechanistic exploration towards developing new anticancer leads derived from the cannabichromene scaffold.