Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines.
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).
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China; Faculty of Chemical Engineering, Industry University of Hochiminh City, Vietnam.
Van-Son
VS
Nguyen
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.
Ling
L
Shi
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.
Fang-Qian
FQ
Luan
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P R China.
Qiu-An
QA
Wang
D000970:Antineoplastic Agents / Q000737:chemistry*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D002945:Cisplatin / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D044949:Kaempferols / Q000138:chemical synthesis* / Q000494:pharmacology; D008352:Mannich Bases / Q000737:chemistry*; D008956:Models, Chemical; D010051:Ovarian Neoplasms / Q000473:pathology; D013696:Temperature; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D000970:Antineoplastic Agents; D044949:Kaempferols; D008352:Mannich Bases; C449720:kaempferide; D002945:Cisplatin