Synthesis and Antiproliferative Activity of Prenylated Chalcone Mannich Base Derivatives

Prenylated chalcones xanthohumol (1) and 2′-hydroxy-3,4,4′-trimethoxy-6′-O-prenyl chalcone (2) were synthesized through the Claisen–Schmidt condensation, O-prenylation, and Claisen rearrangement and deprotection respectively, using phloroglucinol and appropriate benzaldehydes as starting materials. Based on the Mannich reaction of prenylated chalcone 1 or 2 with various secondary amines and formaldehyde in acid alcohol solvent, 10 novel prenylated chalcone Mannich base derivatives 3a–3e and 4a–4e were synthesized. Furthermore, all synthetic compounds were evaluated for antiproliferative activities in vitro against four human cancer cell lines (Aspc-1, SUN-5, HepG-2, and HCT-116) by MTT assay. The results showed that most of them exhibit moderate to good antiproliferative activities against the four human cancer cells with IC50 values of 2.52 to 47.67 μM.