147059-75-4

147059-75-4 structure

Name: Trovafloxacin Mesylate
Chemical Name: trovafloxacin mesylate
CAS Number: 147059-75-4
Molecular Formula: C₂₁H₁₉F₃N₄O₆S
Molecular Weight: 512.45900
Catalog: Signaling Pathways Anti-infection Bacterial
Create Date: 2018-03-07 08:00:00
Modify Date: 2024-01-03 19:30:12
Trovafloxacin mesylate is a broad-spectrum quinolone antibiotic with potent activity against Gram-positive, Gram-negative and anaerobic organisms. Trovafloxacin mesylate blocks the DNA gyrase and topoisomerase IV activity. Trovafloxacin mesylate is also a potent, selective and orally active pannexin 1 channel (PANX1) inhibitor with an IC50 of 4 μM for PANX1 inward current. Trovafloxacin mesylate does not inhibit connexin 43 gap junction or PANX2. Trovafloxacin mesylate leads to dysregulated fragmentation of apoptotic cells by inhibiting PANX1[1][2][3].

Name	trovafloxacin mesylate
Synonyms	Trovafloxacin mesylate,7-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hex-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacidmesylate Trovafloxacin Mesylate Trovafloxacin mesylate

Description	Trovafloxacin mesylate is a broad-spectrum quinolone antibiotic with potent activity against Gram-positive, Gram-negative and anaerobic organisms. Trovafloxacin mesylate blocks the DNA gyrase and topoisomerase IV activity. Trovafloxacin mesylate is also a potent, selective and orally active pannexin 1 channel (PANX1) inhibitor with an IC50 of 4 μM for PANX1 inward current. Trovafloxacin mesylate does not inhibit connexin 43 gap junction or PANX2. Trovafloxacin mesylate leads to dysregulated fragmentation of apoptotic cells by inhibiting PANX1[1][2][3].
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> Topoisomerase Research Areas >> Infection Signaling Pathways >> Anti-infection >> Bacterial
Target	IC50: 4 μM (Pannexin 1 channel (PANX1))[2] Gram-positive, Gram-negative and anaerobic organisms[3] DNA gyrase[3] Topoisomerase IV[3]
In Vitro	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[1]. Trovafloxacin (20 µM; 24 hours; HepG2 cells) and TNF (4 ng/mL) incubation increases expression of early NF-κB-related factors A20 and IκBα[1]. Trovafloxacin prolongs TNF-induced activation of MAPKs and IKKα/β activation in HepG2[1]. 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[2]. 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[3]. Apoptosis Analysis[1] 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[1] 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.
In Vivo	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[1]. 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[1]. Animal Model: Male C57BL/6 J mice (9-11-week-old) injected with recombinant murine TNF ion[1] Dosage: 150 mg/kg Administration: Oral administration; once Result: Showed a greater number of cells with increased nuclear/cytoplasmic p65 ratio in liver.
References	[1]. Giustarini G, et al. The hepatotoxic fluoroquinolone trovafloxacin disturbs TNF- and LPS-induced p65 nuclear translocation in vivo and in vitro. Toxicol Appl Pharmacol. 2020 Mar 15;391:114915. [2]. Poon IK, et al. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. 2014 Mar 20;507(7492):329-34. [3]. Gootz TD, et al. Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus pneumoniae selected in vitro. Antimicrob Agents Chemother. 1996 Dec;40(12):2691-7.

Boiling Point	630.5ºC at 760mmHg
Melting Point	>250 °C (dec.)
Molecular Formula	C₂₁H₁₉F₃N₄O₆S
Molecular Weight	512.45900
Flash Point	335.1ºC
Exact Mass	512.09800
PSA	164.20000
LogP	3.24460
Vapour Pressure	2.59E-24mmHg at 25°C

Symbol	GHS05, GHS08
Signal Word	Danger
Hazard Statements	H314-H361
Precautionary Statements	P280-P305 + P351 + P338-P310
Hazard Codes	C
Risk Phrases	63-34
Safety Phrases	26-36-45
RIDADR	UN 1759 8 / PGIII
RTECS	QN2791250

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