曲伐沙星甲磺酸盐

生物活性靶点体外研究体内研究

曲伐沙星甲磺酸盐

CAS号:147059-75-4
英文名:Trovafloxacin Mesylate
中文名:曲伐沙星甲磺酸盐
CBNumber:CB31456463
分子式:C21H19F3N4O6S
分子量:512.46
MOL File:147059-75-4.mol

曲伐沙星甲磺酸盐化学性质

熔点 :>250°C (dec.)
储存条件 :room temp
溶解度 :DMSO: >10mg/mL
形态 :powder
颜色 :white to off-white

安全信息

危险品标志 :C
危险类别码 :63-34
安全说明 :26-36-45
危险品运输编号 :UN 1759 8 / PGIII
WGK Germany :3
RTECS号 :QN2791250
毒性 :women,LDLo,oral,2mg/kg (2mg/kg),SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE",Archives of Internal Medicine. Vol. 159, Pg. 2225, 1999.

曲伐沙星甲磺酸盐性质、用途与生产工艺

生物活性 Trovafloxacin mesylate 是一种广谱喹诺酮类抗生素，对革兰氏阳性，革兰氏阴性和厌氧菌具有有效的活性。Trovafloxacin mesylate 可阻断 DNA 促旋酶 (DNA gyrase) 和拓扑异构酶 IV (topoisomerase IV) 的活性。Trovafloxacin mesylate 也是一种有效的，选择性的，口服活性的 Pannexin 1 通道 (PANX1) 抑制剂，对 PANX1 内向电流的 IC50 为 4 μM。Trovafloxacin mesylate 不抑制连接蛋白 43 间隙连接或 PANX2。Trovafloxacin mesylate 通过抑制 PANX1 导致凋亡细胞碎片失调。
靶点

IC50: 4 μM (Pannexin 1 channel (PANX1))
Gram-positive, Gram-negative and anaerobic organisms
DNA gyrase
Topoisomerase IV

体外研究

Trovafloxacin (20 µM; 24 hours; HepG2 cells) and tumor necrosis factor (TNF; 4 ng/mL) incubation induces apoptosis and increases leakage of lactate dehydrogenase (LDH) in HepG2 cells.
Trovafloxacin (20 µM; 24 hours; HepG2 cells) and TNF (4 ng/mL) incubation increases expression of early NF-κB-related factors A20 and IκBα.
Trovafloxacin prolongs TNF-induced activation of MAPKs and IKKα/β activation in HepG2.
Trovafloxacin is a potent inhibitor of TO-PRO-3 uptake by apoptotic cells. Trovafloxacin also inhibits ATP release from apoptotic cells. Trovafloxacin does not inhibit caspase 3/7 activation, or caspase-mediated PANX1 cleavage during apoptosis.
Trovafloxacin is equally active against both penicillin-susceptible and -resistant pneumococci, with MICs of 0.06-0.25 mg/mL reported for more than 700 isolates. The MICs of Trovafloxacin at which 90% of isolates are inhibited for 55 isolates of pneumococci is 0.125 μg/mL.

Apoptosis Analysis

Cell Line:	HepG2 cells
Concentration:	20 µM
Incubation Time:	24 hours
Result:	Showed a gradual increase of Annexin V-staining and an increased leakage of lactate dehydrogenase (LDH) at 24 h.

RT-PCR

Cell Line:	HepG2 cells
Concentration:	20 µM
Incubation Time:	24 hours
Result:	Caused a higher increase in the transcription of A20 and IκBα in HepG2 cells.

体内研究

Trovafloxacin (150 mg/kg; oral administration; male C57BL/6 J mice) treatment disrupts TNF-induced p65 nuclear translocation. Trovafloxacin treatment increases expression of early NF-κB-related factors A20 and IκBα.
Trovafloxacin, when administered in combination with lipopolysaccharide (LPS) or TNF to mice induces severe liver toxicity associated with vast apoptotic areas in the liver, increased serum levels of alanine amino transferases (ALT) and pro-inflammatory cytokines.

Animal Model:	Male C57BL/6 J mice (9-11-week-old) injected with recombinant murine TNF ion
Dosage:	150 mg/kg
Administration:	Oral administration; once
Result:	Showed a greater number of cells with increased nuclear/cytoplasmic p65 ratio in liver.