Background: Prenyl flavonoid icaritin (1) and β-anhydroicaritin (2) are two natural products with important
biological and pharmacological effects. such as antiosteoporosis, estrogen regulation and antitumor properties.
Objective: The present study investigates the synthesis and cytotoxic activities on three Human cancer cell lines (Hela,
HCC1954 and SK-OV-3) of icaritin and β-anhydroicaritin Mannich base derivatives in vitro models.
Method: Preylated flavonoid icaritin (1) upon treatment with formic acid under microwave assistance gave another
natural product β-anhydroicaritin (2) in good yield (89%). Based on Mannich reaction of 1 or 2 with various secondary
amines and formaldehyde, two series eighteen new 6-aminomethylated flavonoids Mannich base derivatives 3-11 and
12-20 were synthesized. Their cytotoxic potential against three human cancer cell lines (Hela, HCC1954 and SK-OV-3)
were evaluated by the standard MTT method with cis-Platin and Paclitaxel as positive control.
Results: Our research showed that most of these flavonoid Mannich base derivatives displayed equal or higher (lower
IC50 values) cytotoxic activities than the positive control cis-Platin. Some compounds possess the IC50 value below 10µM. Compounds 6-(diisopropylamino)methyl- and 6-morpholinylmethyl substituted β-anhydroicaritin (15 and 19)
showed selective cytotoxicity against HCC1954 cells (IC50 12.688 µM) and Hela cells (IC50 6.543 µM) respectively.
Conclusion: Our finding most of icaritin and β-anhydroicaritin Mannich base derivatives possessing moderate to
potent cytotoxicity against these three cancer cells (Hela, HCC1954 and SK-OV-3). Compound 15 and 19 showed
selective cytotoxicity against HCC1954 cells and Hela cells respectively, they are potential and selective anticancer
agent and worthy of further development.