Design, synthesis, antibacterial and anti-cell proliferation activities of 1,2,4triazino3,4-h 1,8naphthyridine-8-one-7-carboxylic acid derivatives.
- Author:
Liu-zhou GAO
;
Tao LI
;
Suo Xie YU
;
Wen-long HUANG
;
Hui ZHAO
;
Guo-qiang HU
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Bacterial Agents;
chemical synthesis;
chemistry;
Antineoplastic Agents;
chemical synthesis;
chemistry;
Carboxylic Acids;
Carcinoma, Hepatocellular;
Cell Line;
Cell Proliferation;
Drug Design;
Escherichia coli;
drug effects;
Fluoroquinolones;
chemical synthesis;
chemistry;
HL-60 Cells;
Humans;
Leukemia L1210;
Liver Neoplasms;
Methicillin-Resistant Staphylococcus aureus;
drug effects;
Mice;
Naphthyridines;
Triazines
- From:
Acta Pharmaceutica Sinica
2015;50(3):332-336
- CountryChina
- Language:Chinese
-
Abstract:
To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.
