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[Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].
- Source :
-
Yao xue xue bao = Acta pharmaceutica Sinica [Yao Xue Xue Bao] 2012 Jan; Vol. 47 (1), pp. 66-71. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
CHO Cells
Cell Line, Tumor
Ciprofloxacin pharmacology
Cricetinae
Cricetulus
Fluoroquinolones chemistry
Fluoroquinolones pharmacology
HL-60 Cells
Humans
Inhibitory Concentration 50
Leukemia L1210 pathology
Mice
Structure-Activity Relationship
Thiadiazines chemistry
Thiadiazines pharmacology
Triazoles chemistry
Triazoles pharmacology
Antineoplastic Agents chemical synthesis
Fluoroquinolones chemical synthesis
Thiadiazines chemical synthesis
Triazoles chemical synthesis
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0513-4870
- Volume :
- 47
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Yao xue xue bao = Acta pharmaceutica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 22493807