Bithionol is a potent sAC-specific inhibitor with IC50 value of 4μM[3]. Bithionol inhibited ATP production by working as a classical uncoupler in mitochondria isolated from mouse brain[4].
作用机制
Bithionol binds to the sAC-specific, allosteric binding site for the physiological activator. It induces rearrangements of substrate binding residues and of Arg176, a trigger between the active site and allosteric site.[3]
Bithionol/硫氯酚 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Citrullus vulgaris urease (CVU)
376.50 µM
1 hour
Inhibition of CVU activity, IC50 value of 376.50 μM
Molecules. 2016 Nov 26;21(12):1628.
Rat locus coeruleus neurons
1-10 µM
10 minutes
Potentiated glutamate-induced post-activation inhibition (PAI) in a concentration-dependent manner, without altering glutamate-induced activation
Br J Pharmacol. 2009 Feb;156(4):649-61.
KG-1a cells
7, 14, 28 µM
12, 24, 48, 72 hours
To evaluate bithionol-induced DNA fragmentation and cell cycle arrest, showing an increased proportion of sub-G0/G1 phase cells.
Cell Death Discov. 2024 Aug 29;10(1):390.
MRSA MW2
8, 16, 32 μg/mL
2 hours
To evaluate the bactericidal activity of Bithionol against MRSA MW2 persister cells, results showed complete eradication within 2 hours.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16529-16534.
Neuro2A cells
10 µM
2 hours
Inhibition of NAPE-PLD activity, significantly reducing synaptamide production
Int J Mol Sci. 2020 Nov 20;21(22):8768.
MRSA MW2
8, 16, 32 μg/mL
24 hours
To evaluate the bactericidal activity of Bithionol against MRSA MW2 biofilm persister cells, results showed complete eradication within 24 hours.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16529-16534.
Primary cortical neurons
0.5, 5, 10, 20, 50 µM
24 hours
To evaluate the toxicity of Bithionol on cortical neurons and its protective effect against Aβ42-induced toxicity. Results showed that Bithionol was not toxic to neurons at tested concentrations and significantly reversed Aβ42-induced toxicity at 5 and 10 μM.
Neurobiol Dis. 2015 Feb;74:144-57.
Saccharomyces cerevisiae BY4741
0.3, 1, 10, 50 µM
24 hours
To evaluate the fungicidal activity of Bithionol against Saccharomyces cerevisiae, results showed fungicidal effects at low micromolar concentrations.
mBio. 2016 Aug 2;7(4):e01073-16.
Cryptococcus neoformans H99
0.3, 1, 10, 50 µM
24 hours
To evaluate the fungicidal activity of Bithionol against Cryptococcus neoformans, results showed significant fungicidal effects at low micromolar concentrations.
mBio. 2016 Aug 2;7(4):e01073-16.
MRSA MW2
10 μg/mL
3 hours
To evaluate the bactericidal activity of Bithionol against MRSA MW2, results showed complete eradication within 3 hours.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16529-16534.
Mycobacterium abscessus 19977
20 µM
4 days
Screening compounds for antimicrobial activity against M. abscessus, Bithionol showed excellent antibacterial activity
Antibiotics (Basel). 2024 Jun 5;13(6):529.
CV1 monkey kidney cells
30 µM
48 hours
To evaluate the effect of Bithionol on SV40 replication, results showed that Bithionol inhibited viral replication nearly 100-fold
Antiviral Res. 2012 Oct;96(1):70-81.
Mycobacterium abscessus biofilms
128 µg/mL
48 hours
Evaluate the antibiofilm effect of Bithionol, 128 µg/mL could completely eradicate biofilms
Antibiotics (Basel). 2024 Jun 5;13(6):529.
Vero monkey kidney cells
30 µM
5 days
To evaluate the effect of Bithionol on BKV replication, results showed that Bithionol inhibited viral replication by ~70%
Antiviral Res. 2012 Oct;96(1):70-81.
KG-1a, KG-1, Kasumi-1, HL-60 cells
28 µM
72 hours
To evaluate the synergistic effect of bithionol with venetoclax, showing a significant reduction in cell viability.
Cell Death Discov. 2024 Aug 29;10(1):390.
Mycobacterium abscessus clinical isolates
0.625 µM to 2.5 µM
Evaluate the antibacterial activity of Bithionol against different subtypes of M. abscessus
Antibiotics (Basel). 2024 Jun 5;13(6):529.
VRSA VRS1
8, 16, 32 μg/mL
To evaluate the bactericidal activity of Bithionol against VRSA VRS1 persister cells, results showed complete eradication.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16529-16534.
SAC KO mouse embryonic fibroblasts
100 µM
To test the effect of Bithionol on tmAC-dependent cAMP formation, results showed that Bithionol did not inhibit tmAC-dependent cAMP accumulation at concentrations up to 100 μM.
J Biol Chem. 2016 Apr 29;291(18):9776-84.
4-4 cells
50 µM and 100 µM
To test the effect of Bithionol on sAC activity in cellular systems, results showed that Bithionol caused a dose-dependent decrease in cAMP formation with essentially complete inhibition of sAC-dependent cAMP accumulation at 100 μM.
J Biol Chem. 2016 Apr 29;291(18):9776-84.
Bithionol/硫氯酚 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Transgenic mice (mThy1-APPtg)
Alzheimer's disease model
Intraperitoneal injection
10 mg/kg
Daily for 1 month
To evaluate the effects of Bithionol on Aβ deposition, synapse loss, and neuronal damage in APP transgenic mice. Results showed that Bithionol significantly reduced Aβ42 oligomer levels, stabilized diffuse-like plaques, and ameliorated synapse loss, neuronal damage, and astrogliosis.
Neurobiol Dis. 2015 Feb;74:144-57.
Mice
MRSA thigh infection model
Intraperitoneal injection
30 mg/kg
Every 12 hours for 3 days
To evaluate the bactericidal effect of Bithionol in combination with gentamicin against MRSA persister cells, results showed significant reduction in bacterial burden.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16529-16534.
NSG mice
KG-1a cell leukemia xenograft model
Intraperitoneally
50 mg/kg
Once daily for two weeks
To evaluate the inhibitory effect of bithionol on AML growth, showing a significant reduction in the percentage of hCD45+ cells in the bone marrow and peripheral blood.
Cell Death Discov. 2024 Aug 29;10(1):390.
Mice
Intravenous mouse meningoencephalitis model induced by Cryptococcus neoformans H99
Oral gavage
50 mg/kg
Single dose
To evaluate the pharmacokinetics and anti-Cryptococcus neoformans efficacy of Bithionol in mice, results showed limited drug concentrations in brain tissue and limited therapeutic efficacy.
mBio. 2016 Aug 2;7(4):e01073-16.
Bithionol/硫氯酚 动物研究
Dose
Horse: 5 mg/kg, 10 mg/kgEvaluation of Anthelmintic Efficacy of Bithionol Paste against Tapeworms Naturally Infected in Horses, by Fecal Examination and Necropsy[3] (p.o.)
Mice； 30 mg/kg - 240 mg/kg[4] (p.o.)
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