title: [Design, synthesis, antibacterial and anti-cell proliferation activities of [1,2,4]triazino[3,4-h] [1,8]naphthyridine-8-one-7-carboxylic acid derivatives].
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.
authors.forename: Liu-zhou
authors.initials: LZ
authors.lastname: Gao
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Suo
authors.initials: S
authors.lastname: Xie Yu
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Guo-qiang
authors.initials: GQ
authors.lastname: Hu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002264:Carboxylic Acids; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D049109:Cell Proliferation; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D007939:Leukemia L1210; D008113:Liver Neoplasms; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D009287:Naphthyridines; D014227:Triazines
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D024841:Fluoroquinolones; D009287:Naphthyridines; D014227:Triazines