Synthesis and antitumor activity of fluoroquinolone C-3 arylidene thiazolone derivatives from ciprofloxacin
10.16438/j.0513-4870.2019-0036
- VernacularTitle:氟喹诺酮C-3芳苄叉基噻唑酮衍生物的合成与抗肿瘤活性
- Author:
Na WANG
1
;
Hui-li ZHANG
2
;
Chao-ran CHEN
3
;
Wen-long HUANG
4
;
Guo-qiang HU
1
Author Information
1. Institute of Drugs, Henan University, Kaifeng 475001, China
2. School of Pharmacy, Zhengzhou University of Industrial Technology, Zhengzhou 451150, China
3. Institute of Nursing and Health, Henan University, Kaifeng 475004, China
4. Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
- Publication Type:Research Article
- Keywords:
fluoroquinolone;
thiazole;
unsaturated ketone;
bioisostere;
antitumor activity
- From:
Acta Pharmaceutica Sinica
2019;54(4):687-691
- CountryChina
- Language:Chinese
-
Abstract:
To expand an efficient strategy for the conversion of antibacterial activity of fluoroquinolones into an antitumor activity, sixteen new compounds, 1-cyclopropyl-6- fluoro-7-(4-methyl-piperazin-1-yl)-3-(5-arylidene-thiazol-4(5H)-one-2-yl)-quinolon-4(1H)-ones (7a-7p), were designed and synthesized with a thiazolone ring and an arylidene moiety as an isostere and modified group, respectively, from ciprofloxacin. Their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity of the synthesized compounds were measured using Hep-3B, Capan-1 and HL60 cell lines and were found to be more potent than ciprofloxacin. Meanwhile, the SAR revealed that the halogenated phenyl compounds such as fluorophenyl (7h, 7i), chlorophenyl (7j, 7k) or bromophenyl compounds (7l, 7m), and aromatic heterocyclic substitution such as furyl (6n) or pyridyl compounds (6o, 6p) displayed better activity than the control compounds, especially the IC50 values of pyridyl compounds 6o and 6p against Capan-1 cell growth was comparable to doxorubicin. Thus, an arylidene-modified thiazolone scaffold as the replacement of the C-3 carboxylic acid group appears to be an alternative route for an improved antitumor activity of fluoroquinolones.
