Van-Son Nguyen1,2, Ling Shi1, Sheng-Chun Wang1, Qiu-An Wang1. 1. College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China 2. Faculty of Thanh Hoa Campus, Industrial University of Ho Chi Minh City, Vietnam
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.
BACKGROUND:Prenyl flavonoidicaritin (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 Humancancer cell lines (Hela, HCC1954 and SK-OV-3) of icaritin and β-anhydroicaritin Mannich base derivatives in vitro models. METHOD: Preylated flavonoidicaritin (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 flavonoidsMannich base derivatives 3-11 and 12-20 were synthesized. Their cytotoxic potential against three humancancer 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 flavonoidMannich 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.