title: [Part IV. Synthesis and antitumor evaluation of s-triazolothiadiazines and pyrazolo s-triazoles derived from ciproxacin].
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.
authors.affiliation: Institute of Chemistry & Biology, Henan University, Kaifeng 475001, China.
authors.forename: Song-Qiang
authors.initials: SQ
authors.lastname: Xie
authors.forename: Yin-Sheng
authors.initials: YS
authors.lastname: Chen
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Wang
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Duan
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Wen
authors.forename: Tie-Yao
authors.initials: TY
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Hu
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D013829:Thiadiazines; D014230:Triazoles; D002939:Ciprofloxacin