Synthesis of Icaritin and β-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines

Author(s): Van-Son Nguyen, Ling Shi, Sheng-Chun Wang, Qiu-An Wang

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 1 , 2017

Become EABM
Become Reviewer
Call for Editor

Graphical 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.

Keywords: Icaritin, β-anhydroicaritin, Mannich base derivatives, synthesis, cytotoxic activity.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2017
Page: [137 - 142]
Pages: 6
DOI: 10.2174/1871520616666160404111210
Price: $65

Article Metrics

PDF: 58
PRC: 1