title: Synthesis of Icaritin and β-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China|Faculty of Thanh Hoa Campus, Industrial University of Ho Chi Minh City, Vietnam
authors.forename: Van-Son
authors.initials: VS
authors.lastname: Nguyen
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
authors.forename: Ling
authors.initials: L
authors.lastname: Shi
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
authors.forename: Qiu-An
authors.initials: QA
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D005419:Flavonoids; D008352:Mannich Bases; C578157:anhydroicaritin; C499403:icaritin