- 生物活性
Trovafloxacin 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 可阻断 DNA 促旋酶 (DNA gyrase) 和拓扑异构酶 IV (topoisomerase IV) 的活性。Trovafloxacin 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 不抑制 connexin 43 gap junction 或 PANX2。Trovafloxacin 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
Result:
Showed a greater number of cells with increased nuclear/cytoplasmic p65 ratio in liver.
- 化学性质
盐酸特伐沙星(Trovafloxacin Hydrochloride)：C20H15F3N4O3HCl。 [146961-34-4]。从乙腈-甲醇得淡黄色结晶，熔点246℃(分解)。
- 喹诺酮类抗菌药。
医药
450ml THF、50ml水、127ml甲磺酸和7-氯-1-(2，4-二氟苯基)-7-氟-1，4-二氢-4-氧代-1，8-喹啉-3-羧酸乙酯一起回流1h，冷至25℃。过滤收集结晶，用THF洗，真空干燥，得7-氯-1-(2，4-二氟苯基)-7-氟-1，4-二氢-4-氧代-1，8-喹啉-3-羧酸，收率89%，mp 250℃。
500mg 7-氯-1-(2，4-二氟苯基)-7-氟-1，4-二氢-4-氧代-1，8-喹啉-3-羧酸、624mg(1α，5α，6α)-6-氨基-3-氮杂二环[3.1.0]己烷二甲苯磺酸盐、0.6ml三乙胺和5ml甲醇，一起回流16h。过滤收集形成的白色固体，在THF中回流，再过滤收集。得450ml特伐沙星，收率75%，mp 225～228℃(分解)。
