Synthesis and preliminary biological evaluation of polyamine-aniline acridines as P-glycoprotein inhibitors.
We have synthesized a series of polyamine-based anilinoacridine derivatives. The preliminary biological evaluation indicated that the 9-anilinoacridine-polyamine derivatives had low or insignificant in vitro cytotoxicity against K562 cell line and K562/ADM, the drug-resistant cell line. However, the evaluation for P-gp modulation showed that they held potent P-gp inhibitory ability. Among them, the effect of compound 7c on P-gp was even greater than that of Verapamil, the known P-gp modulator. The results suggest that 9-anilinoacridine-polyamine derivatives can be employed as effective P-gp modulators.
Jianhong
J
Wang
Pengfei
P
Cheng
Tianwei
T
Luo
Zhaoyi
Z
Wang
Yahong
Y
Zhang
Key Laboratory of Natural Medicines and Immunotechnology of Henan Province, Henan University, kaifeng 475004, Henan, P.R. China. hdky@henu.edu.cn.
Jin
J
Zhao
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors*; D000677:Amsacrine / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D011073:Polyamines; D000677:Amsacrine; C022202:9-anilinoacridine