90-33-5 Usage
Chemical Properties
Off-White to Yellow Crystals
Originator
Odeston,Merck
Uses
Different sources of media describe the Uses of 90-33-5 differently. You can refer to the following data:
1. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. 4-MU is an already approved drug in Europe and Asia called “hymecromone” where it is used to treat biliary spasm.
4-Methylumbelliferone is useful as an indicator in the determination of nitric acid. It is also useful in the kinetic investigation of enzyme activity. 4-Methylumbelliferone is fluorescent in alkaline solution.
2. Standard for the fluorometric determination of enzyme activity. Highly fluorescent in alkaline solution.
Fluorescence: max Abs. l = 360nm, max. Em. l = 449nm; pH > 9
3. choloretic, spasmolytic, sunscreen, Analytical reagent.
Definition
ChEBI: A hydroxycoumarin that is umbelliferone substituted by a methyl group at position 4.
Manufacturing Process
Resorcin reacted with 3-oxo-butyric acid ethyl ester in the presence sulfuric
acid and phosphorous pentaoxide and 4-methyl-7-hydroxycoumarine
(hymecromone) was obtained.
Therapeutic Function
Choleretic, Spasmolytic, Sunscreen agent
Air & Water Reactions
Insoluble in water.
Fire Hazard
Flash point data for 4-Methylumbelliferone are not available. 4-Methylumbelliferone is probably combustible.
Pharmaceutical Applications
4-Methylumbelliferone is primarily used in synthesizing medicinal compounds and as a building block for fluorescent probes. Applications include synthesis of:
coumarin triazole derivatives as potential antimicrobial agents.
coumarin salen-based fluorescence sensors for Mg2+ detection.
pyranocoumarin derivatives as anti-hyperglycemic and anti-dyslipidemic agents.
coumarin piperazine derivatives as potential multireceptor atypical antipsychotics.
4-methylumbelliferyl T-antigen as a substrate for endo-α-N-acetylgalactosaminidase.
Biological Activity
4-methylumbelliferone is a hyaluronic acid (ha) synthesis inhibitor. the activation of has2 and the over-production of ha are existed in many metastatic tumor cell lines. increased synthesis of ha is often associated with increased metastatic potential and invasivity in tumor cells.
Safety Profile
Moderately toxic by
ingestion and intraperitoneal routes. An
experimental teratogen. Experimental
reproductive effects. When heated to
decomposition it emits acrid smoke and
irritating fumes.
in vitro
4-methylumbelliferone (mu), an inhibitor of ha synthesis, has been studied as a potential anti-tumor drug on account of inhibiting the growth of primary tumors and distant metastasis of tumor cells. the mechanism still needs to be clarified, although several studies revealed that the anticancer effects of mu are mediated by inhibition of ha signal pathway. in a previous study the regulation of ha synthesis was demonstrated by ceramide, and now show how mu activated nsmase2 generates ceramides and mediates mu modulated inhibition of ha synthesis (cell migration and invasion, and apoptosis of tumor cells). using a ha enriched mouse oligodendroglioma cell line g26-24, it was found that mu elevated the activity of nsmase2 and enhanced ceramide levels, which in turn potentiated phosphatase pp2a activity. further, the activated pp2a decreased phosphorylation of akt, reduced activities of ha synthase2 (has2) and calpains, and blocked both the synthesis of ha, and the migration and invasion of g26-24 tumor cells. in addition, mu mediated ceramide induced activation of p53 and caspase-3, decreased sirt1 expression and deduced g26-24 viability. the mechanism of the mu anticancer therefore initially involves nsmase2/ceramide/pp2a/akt/has2/caspase-3/p53/sirt1 and the calpain signaling pathway, indicating that ceramides play a important role in the ability of a tumor to become aggressively metastatic and grow [1].
Purification Methods
Purify it by recrystallisation from EtOH. It is very slightly soluble in cold H2O (solubility at 37o is 0.22%), slightly soluble in Et2O and CHCl3, but soluble in MeOH and AcOH. It has a blue fluorescence in aqueous EtOH and has UV: 221, max 251 and 322.5nm (MeOH). The IR has 3077 br, 1667, 1592, 1385, 1267, 1156, 1130 and 1066 cm-1.max The acetate has m 153-154o. [Woods & Sapp J Org Chem 27 3703 1962, Beilstein 18 III/IV 332, 18/1 V 439.]
references
[1] qin j, kilkus j, dawson g. the hyaluronic acid inhibitor 4-methylumbelliferone is an nsmase2 activator-role of ceramide in mu anti-tumor activity. biochim biophys acta. 2016 feb;1861(2):78-90.
Check Digit Verification of cas no
The CAS Registry Mumber 90-33-5 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 9 and 0 respectively; the second part has 2 digits, 3 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 90-33:
(4*9)+(3*0)+(2*3)+(1*3)=45
45 % 10 = 5
So 90-33-5 is a valid CAS Registry Number.
InChI:InChI=1/C10H8O3/c1-6-4-10(12)13-9-5-7(11)2-3-8(6)9/h2-5,11H,1H3
90-33-5Relevant articles and documents
Prostate-Specific Membrane Antigen-Targeted Turn-on Probe for Imaging Cargo Release in Prostate Cancer Cells
Abbasi, Armina,Berkman, Clifford E.,Caromile, Leslie A.,Lovingier, Christine L.,Mesbahi, Nooshin,Olatunji, Feyisola P.,Panteah, Mylan,Savoy, Emily A.,Talley, Cresencia M.
, p. 2386 - 2396 (2021/11/16)
The tunable nature of phosphoramidate linkers enables broad applicability as pH-triggered controlled-release platforms, particularly in the context of antibody-and small-molecule-drug conjugates (ADCs and SMDCs), where there remains a need for new linker technology. Herein, we explored in-depth the release of turn-on fluorogenic payloads from a homoserinyl-based phosphoramidate acid-cleavable linker. Kinetics of payload release from the scaffold was observed in buffers representing the pH conditions of systemic circulation, early and late endosomes, and lysosomes. It was found that payload release takes place in two key consecutive steps: (1) P-N bond hydrolysis and (2) spacer immolation. These two steps were found to follow pseudo-first-order kinetics and had opposite dependencies on pH. P-N bond hydrolysis increased with decreasing pH, while spacer immolation was most rapid at physiological pH. Despite the contrasting release kinetics of these two steps, maximal payload release was observed at the mildly acidic pH (5.0-5.5), while minimal payload release occurred at physiological pH. We integrated this phosphoramidate-payload linker system into a PSMA-targeted fluorescent turn-on probe to study the intracellular trafficking and release of a fluorescent payload in PSMA-expressing prostate cancer cells. Results showed excellent turn-on and accumulation of the coumarin payload in the late endosomal and lysosomal compartments of these cells. The release properties of this linker mark it as an attractive alternative in the modular design of ADCs and SMDCs, which demand selective intracellular payload release triggered by the pH changes that accompany intracellular trafficking.
Nanostructured coumarin-based cobalt complex as an efficient, heterogeneous and recyclable catalyst for the three-component synthesis of benzo[b]pyran and 3,4-dihydropyrano[c]chromene derivatives
Sharghi, Hashem,Razavi, Seyyede Faeze,Aberi, Mahdi,Sabzalizadeh, Fatemeh,Karbalaei-Heidari, Hamid Reza
, p. 1641 - 1655 (2021/01/09)
Abstract: An improved one-pot three-component reaction of carbonyl compounds (dimedon, 4-hydroxy coumarin and 1,3-cyclohexadion) with malononitrile and aryl aldehydes in aqueous media (H2O:EtOH) as a solvent with short reaction time for the synthesis of benzo[b]pyran and 3,4- dihydropyrano[c]chromane derivatives by using nanostructured coumarin-based cobalt complex as an efficient heterogeneous catalyst. The salient features of this new protocol include simple procedure, high yields, easy isolation of products without need to column chromatography and short reaction times. Also, the nanocatalyst was recovered by adding EtOH and reused five times without significant loss of its catalytic activity. Biological impact assessments of the complex were conducted by DNA cleavage ability assay and eukaryotic cell toxicity measurement. Although the complex showed single-strand DNA breakage under oxidative conditions, its high polar nature revealed a marked decrease in cell toxicity data due to the restriction on cell entry. Graphic abstract: [Figure not available: see fulltext.]
Identification of inhibitors targeting polyketide synthase 13 of Mycobacterium tuberculosis as antituberculosis drug leads
Wang, Xiao,Zhao, Wenting,Wang, Bin,Ding, Wei,Guo, Hao,Zhao, Hongyi,Meng, Jianzhou,Liu, Sihan,Lu, Yu,Liu, Yishuang,Zhang, Dongfeng
, (2021/06/30)
Polyketide synthase 13 (Pks13) is an essential enzyme in the synthesis of mycolic acids in Mtb. Therefore, Pks13 is a promising drug target for tuberculosis treatment. We used a structure-guided approach to identify novel chemotype inhibitors of Pks13 and assessed them using a Pks13 enzymatic assay and surface plasmon resonance. The structure–activity relationships (SAR) results demonstrated that the substituents at the 2, 5, and 6 positions of the 4H-chromen-4-one scaffold are critical for maintaining the MIC. Compound 6e with 2-hydroxyphenyl at the 2 position of the 4H-chromen-4-one scaffold, exhibited potent activity against Mtb H37Rv (MIC = 0.45 μg/mL) and displayed good Pks13 affinity and inhibition (IC50 = 14.3 μM). This study described here could provide an avenue to explore a novel inhibitor class for Pks13 and aid the further development of antituberculosis drugs.
