Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.

Van-Son Nguyen; Ling Shi; Fang-Qian Luan; Qiu-An Wang

Van-Son Nguyen College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China; Faculty of Chemical Engineering, Industry University of Hochiminh City, Vietnam.;
Ling Shi College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.;
Fang-Qian Luan College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.;
Qiu-An Wang College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.;

Abstract

Kaempferide (3,5,7-trihydroxy-4'-methoxyflavone, 1), a naturally occurring flavonoid with potent anticancer activity in a number of human tumour cell lines, was first semisynthesized from naringin. Based on Mannich reaction of kaempferide with various secondary amines and formaldehyde, nine novel kaempferide Mannich base derivatives 2-10 were synthesized. The aminomethylation occurred preferentially in the position at C-6 and C-8 of the A-ring of kaempferide. All the synthetic compounds were tested for antiproliferative activity against three human cancer cell lines (Hela, HCC1954, SK-OV-3) by the standard MTT method. The results showed that compounds 1, 2 and 5-10 were more potent against Hela cells with IC50 values of 12.47-28.24 μM than the positive control cis-platin (IC50 41.25 μM), compounds 5, 6, 8 and 10 were more potent against HCC1954 cells with IC50 values of 8.82-14.97 μM than the positive control cis-platin (IC50 29.68 μM), and compounds 2, 3, 5, 6 and 10 were more potent against SK-OV-3 cells with IC50 values of 7.67-18.50 μM than the positive control cis-platin (IC50 21.27 μM).