Title:Synthesis of Icaritin and β-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines
VOLUME: 17 ISSUE: 1
Author(s):Van-Son Nguyen, Ling Shi, Sheng-Chun Wang and Qiu-An Wang
Affiliation:Technology Faculty of Thanh Hoa Campus, Industrial University of Ho Chi Minh City, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082
Keywords:Icaritin, β-anhydroicaritin, Mannich base derivatives, synthesis, cytotoxic activity.
Abstract: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.
