Synthesis and anticancer activity of novel quinoline-docetaxel analogues.
A series of novel quinoline-docetaxel analogues (6a-6g, 13a-13g) were designed and synthesized by introducing bioactive quinoline scaffold to C2'-OH of docetaxel. The anticancer activities of these novel analogues were investigated against different human cancer cell lines including Hela, A549, A2780, MCF-7 and two resistant strains A2780-MDR and MCF-7-MDR. The data showed these analogues possessed similar to better cytotoxicity than docetaxel. Compound 6c was found to be the most potent one, and its IC50 value against MCF-7-MDR was 8.8 nM (IC50 of docetaxel was 180 nM). The work indicated that the introduction of quinolyl group in docetaxel could enhance cytotoxicity and reduce drug-resistance.
Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle Road, Xian 710032, People's Republic of China.
Ming
M
Chen
Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle Road, Xian 710032, People's Republic of China.
Hui
H
Chen
Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle Road, Xian 710032, People's Republic of China.
Jiangwei
J
Ma
Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle Road, Xian 710032, People's Republic of China. Electronic address: wqwlxy@fmmu.edu.cn.
Xueying
X
Liu
Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle Road, Xian 710032, People's Republic of China. Electronic address: syzhang@fmmu.edu.cn.
Shengyong
S
Zhang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011804:Quinolines; D043823:Taxoids; D000077143:Docetaxel; C037219:quinoline
Anticancer; Cytotoxicity; Docetaxel; Drug-resistance; Quinoline