Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin.
- Author:
Song-Qiang XIE
1
;
Yin-Sheng CHEN
;
Guo-Qiang WANG
;
Nan-Nan DUAN
;
Xiao-Yi WEN
;
Tie-Yao CAO
;
Jun YIN
;
Wei WANG
;
Guo-Qiang HU
;
Wen-Long HUANG
Author Information
1. Institute of Chemistry & Biology, Henan University, Kaifeng 475001, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
chemical synthesis;
chemistry;
pharmacology;
CHO Cells;
Cell Line, Tumor;
Ciprofloxacin;
pharmacology;
Cricetinae;
Cricetulus;
Fluoroquinolones;
chemical synthesis;
chemistry;
pharmacology;
HL-60 Cells;
Humans;
Inhibitory Concentration 50;
Leukemia L1210;
pathology;
Mice;
Structure-Activity Relationship;
Thiadiazines;
chemical synthesis;
chemistry;
pharmacology;
Triazoles;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2012;47(1):66-71
- CountryChina
- Language:Chinese
-
Abstract:
An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.
