338967-87-6 Usage
Description
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone is a quinazolinone derivative with a complex chemical structure, featuring a 2,4-dichloro-5-methoxyphenyl group attached to the 3-position of the quinazolinone core. 3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone exhibits a range of biological activities and potential applications across various industries.
Description
Mdivi-1, also known as Mitochondrial Division Inhibitor 1, is a quinazolinone derivative that exhibits cell permeability and the ability to traverse the blood-brain barrier. It has been shown to provide protective effects in heart and brain ischemia-reperfusion injury.
Uses
Used in Pharmaceutical Industry:
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone is used as a pharmaceutical compound for its potential therapeutic effects. 3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone's unique structure and properties make it a candidate for the development of new drugs targeting various diseases.
Used in Chemical Research:
In the field of chemical research, 3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone serves as a valuable compound for studying the structure-activity relationships of quinazolinone derivatives. Its synthesis and modification can provide insights into the design of novel bioactive molecules.
Used in Material Science:
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone may also find applications in material science, particularly in the development of new materials with specific properties. 3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone's chemical structure could be exploited to create materials with tailored characteristics for various applications.
For example, the result for Mdivi-1 is:
Uses
Used in Inhibiting Mitochondrial Division:
Mdivi-1 is used as an inhibitor of mitochondrial division, specifically targeting the GTPase activity of dynamin-related protein 1 (DRP1) and Dynamin I. It is effective in inhibiting cell migration and proliferation in various cell types, such as embryonic thoracic aorta A7r5 cells.
Used in Cell Biology Research:
Mdivi-1 is employed in cell biology research for studying mitochondrial network reshaping and reactive oxygen species (ROS) production in cells, such as oligodendrocyte precursor cells (OPCs).
Used in Inducing Mitochondrial Damage:
In lung fibroblasts, Mdivi-1 is used to induce mitochondrial damage, which can be useful for understanding the role of mitochondria in cellular processes and the development of potential therapeutic strategies.
Used in Ischemia-Reperfusion Injury Studies:
Mdivi-1 is utilized in Langendorff isolated perfused rat heart models of ischemia-reperfusion injury to decrease doxorubicin-induced increases in infarct-to-risk ratios, demonstrating its potential in protecting against heart damage.
Used in Acute Lung Injury Treatment:
In a mouse model of LPS-induced acute lung injury, Mdivi-1 is used to reduce the severity of lung injury when administered at a specific dose, highlighting its potential therapeutic application in treating lung injuries.
Biological Activity
Mdivi-1 (Mitochondrial division inhibitor 1) is a selective and cell-penetrating inhibitor of mitochondrial division, inhibits DRP1 (dynamin-related GTPase) and Dynamin I (Dnm1) with IC50 of 1-10 μM. Mdivi-1 reduces mitophagy and increases apoptosis.
Biochem/physiol Actions
Mdivi-1 is a cell-permeable selective inhibitor of mitochondrial division DRP (dynamin-related GTPase) and inhibitor of the mitochondrial division dynamin (Dnm1). Mitochondrial fusion and division play important roles in the regulation of apoptosis. Mdivi-1 is the first selective inhibitor of mitochondrial division dynamins. In principle, Mdivi-1 represents a class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases.
in vivo
The protein expression of Drp1 and GFAP is significantly increased during early neural development in the retina of ischemic mice. The use of Mdivi-1 blocked apoptosis in the ischemic retina and significantly increased RGC survival after two weeks of ischemia. In normal mouse retina, the expression of Drp1 is mainly distributed in the ganglion cell layer (GCL), the inner plexiform layer, the inner nuclear layer (INL) and the outer plexiform layer. In the ganglion cell layer, Drp1 is strongly immunoreactive. Drp1 protein expression was increased in GCLs 12 h after ischemia induction. Mdivi-1 did not alter the increase in Drp1 protein expression but significantly decreased GFAP protein expression.
in vitro
Mdivi-1 is a membrane-crossing quinazolone that inhibits the cleavage of DRPs (dynamin-associated GTPases) by yeast Dnm1 and human Drp1, and induces mitochondrial fusion into a nest-like structure efficiently and reversibly. Extracellular studies suggest that mdivi-1 blocks the ATPase activity (IC50<10 μM) and self-assembly of Dnm1 through allosteric regulation. Mdivi-1 potently inhibited STS and C8-Bid-induced MOMP (increased mitochondrial outer membrane permeability) in HeLa cells and extracellular murine hepatocyte mitochondrial preparations, respectively. In cells, mdivi-1 further inhibited apoptosis by inhibiting mitochondrial outer membrane permeability. In general, mivi-1 represents a class of therapies for the treatment of stroke, myocardial infarction and neurodegenerative diseases.
References
1) Cassidy-Stone et al. (2008), Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization; Dev. Cell, 14 193
2) Lackner et al. (2010), Small molecule inhibitors of mitochondrial division: tools that translate basic biological research into medicine; Chem. Biol., 17 578
Check Digit Verification of cas no
The CAS Registry Mumber 338967-87-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,3,8,9,6 and 7 respectively; the second part has 2 digits, 8 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 338967-87:
(8*3)+(7*3)+(6*8)+(5*9)+(4*6)+(3*7)+(2*8)+(1*7)=206
206 % 10 = 6
So 338967-87-6 is a valid CAS Registry Number.
338967-87-6Relevant articles and documents
Development of 2-thioxoquinazoline-4-one derivatives as dual and selective inhibitors of dynamin-related protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA)
Numadate, Akiyoshi,Mita, Yusuke,Matsumoto, Yotaro,Fujii, Shinya,Hashimoto, Yuichi
, p. 979 - 988 (2015/02/19)
An established inhibitor ot dynamin-related protein 1 (Drp1), 3-(2,4-dichloro-5-methoxyphenyl)- 2- thioxoquinazoline-4-one (mdivi-1), was recently reported also to show potent puromycin-sensitive aminopeptidase (PSA)-inhibitory activity. Herein, we report structural development of mdivi-1 derivatives and structure-activity relationship (SAR) analysis of the synthesized compounds, as well as the structurally related PSA-specific inhibitor 3-(2,6-diethylphenyl)quinazoline-2,4-dione (PAQ-22), with the aim of identifying key structural features for inhibitory activity in order to develop selective inhibitors of Drpl, which is a potential target for treatment of Huntington's disease. Among the synthesized compounds, 3-(4-chloro3methoxyphenyl)-2-thioxoquinazoline-4-one 10g) exhibited more potent Drpl-inhibitory activity than mdivi-1 with high selectivity for Drpl over PSA.
