Synthesis and anti-proliferative activity of fluoroquinolone C-3 fused heterocyclic α,β-unsaturated ketones derived from ciprofloxacin.
- Author:
Taol LI
;
Zhou Gao LIU
;
Yu-suo XIE
;
Yan-fei FENG
;
Qiang YAN
;
Shu-min WU
;
Li-li NI
;
Hui ZHAO
;
Wen-long HUANG
;
Guo-qiang HU
- Publication Type:Journal Article
- MeSH:
Anti-Bacterial Agents;
Antineoplastic Agents;
chemical synthesis;
pharmacology;
Cell Line, Tumor;
Ciprofloxacin;
analogs & derivatives;
Fluoroquinolones;
chemical synthesis;
pharmacology;
HL-60 Cells;
Humans;
Ketones;
pharmacology;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2015;50(5):569-573
- CountryChina
- Language:Chinese
-
Abstract:
To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.
