1. [Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].
- Author
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Xie SQ, Chen YS, Wang GQ, Duan NN, Wen XY, Cao TY, Yin J, Wang W, Hu GQ, and Huang WL
- 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
- 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.
- Published
- 2012