Synthesis and biological activity of anthrapyrazoles derivatives as potential antitumor agents.
We have synthesized a series of anthrapyrazoles derivatives. The biological results indicated that these derivatives exhibited potent in vitro cytotoxicity against different cancer cell lines (human hepatocellular carcinoma HepG2 and BEL-7402, human colonic carcinoma HCT-116 and HT-29) and drug-resistant human hepatoma cell line (SMMC-7721). Among them, the polyamine-based anthrapyrazole derivatives 4c and 4f-g showed superior cytotoxicity than that of Mitoxantrone both on cancer cell lines and the drug-resistant subline. However, the DNA relaxation assay revealed that they had insignificant topoisomerase II inhibition. These results clearly indicate that polyamine side chains will have a profound effect on the cytotoxicity of anthrapyrazoles derivatives.
Jianhong
J
Wang
Huijun
H
Zhao
Zhaoyang
Z
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
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D008942:Mitoxantrone / Q000737:chemistry; D009928:Organ Specificity; D011073:Polyamines / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000880:Anthraquinones; D000970:Antineoplastic Agents; D011073:Polyamines; D011720:Pyrazoles; D008942:Mitoxantrone; D004250:DNA Topoisomerases, Type II