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Chemical Structure| 288-32-4 Chemical Structure| 288-32-4

Structure of Imidazole
CAS No.: 288-32-4

Chemical Structure| 288-32-4

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Imidazole is a widely used organic compound with various biological activities, including serving as an enzyme inhibitor and drug precursor. Imidazole is mainly used in biocatalysis, drug synthesis, and as an inhibitor of various enzymes (e.g., heparinase and some bacterial enzymes). It is also utilized in research to study enzyme mechanisms and drug actions.

Synonyms: 1,3-Diaza-2,4-cyclopentadiene; Glyoxaline

4.5 *For Research Use Only !

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Product Citations

Product Citations      Show More

Williams, Michael J ; Ronayne, Conor T ; Schumacher, Tanner J ; Johnson, Kayla M ; Wittmer, Mattew D ; Johnson, Joseph L , et al.

Abstract: Reprogrammed cancer cell proliferation requires high levels of protein synthesis and concomitant folding and processing. N-terminal methionine amino peptidases (MetAP) are a class of enzymes that cleave the initiator methionine amino acids to allow for peptide maturation and co-translational processing. Specifically, based on its role in protein synthesis, MetAP2 has been found to be upregulated in cancer cells and has been explored as a potential anticancer target. Cellular perturbations that impinge on protein synthesis activate cellular stress pathways, including the integrated stress response and mTORC1. Nitroxoline, a MetAP2 inhibitor has been explored as an anticancer agent but is hampered by poor pharmacokinetic properties. Here, we synthesize a few O-substituted silyl and nonsilyl nitroxoline analogs to diversify the nitroxoline template to reduce metabolic vulnerability. In vitro MetAP2 and cancer cell proliferation inhibition assays demonstrate that synthesized analogs retain potency when compared to the parent nitroxoline. Mechanistically, we show that the lead candidate compound 3 and nitroxoline activate ATF4 mediated stress responses through non-canonical mTORC1. These results further implicate MetAP2 protein processing in mTORC1 nutrient sensing pathways and provide novel synthetic analogs of nitroxoline for potential cancer treatment.

Keywords: nitroxoline ; MetAP2 ; integrated stress response ; ATF4 ; mTORC1

Purchased from AmBeed: ; ; ;

Chandra, Shambhu Deo ; Gunasekera, Shanal ; Noichl, Benjamin Philipp ; Patrick, Brian O ; Perrin, David M ;

Abstract: We report a streamlined synthesis of (2S,3R,4R)-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.

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Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto ; Prathamesh M. Datar ; Daniel J. DiRocco ; Katherine Huntera and E. Neil G. Marsh

Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.

Nguyen, Long T. ; Rananaware, Santosh R. ; Yang, Lilia G. ; Macaluso, Nicolas C. ; Ocana-Ortiz, Julio E. ; Meister, Katelyn S. , et al.

Abstract: CRISPR-Cas-based diagnostics have the potential to elevate nucleic acid detection. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify the workflow and reduce carryover contamination. Here, we report an engineered Cas12b with improved thermostability that falls within the optimal temperature range (60°C-65°C) of reverse transcription-loop-mediated isothermal amplification (RT-LAMP). Using de novo structural analyses, we introduce mutations to wild-type BrCas12b to tighten its hydrophobic cores, thereby enhancing thermostability. The one-pot detection assay utilizing the engineered BrCas12b, called SPLENDID (single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting. We validate SPLENDID clin. in 80 serum samples for hepatitis C virus (HCV) and 66 saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and accuracy. We obtain results in as little as 20 min, and with the extraction process, the entire assay can be performed within an hour.

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Emily Penn ; Antonio Baclig ; Devi Ganapathi ; William C. Chueh ;

Abstract: Eutectic electrolytes can attain high concentrations of redox-active species, offering a path toward high energy density redox flow batteries. Here we introduce a new entropically-driven eutectic mixing approach using organic small molecules. By mixing chemically similar redox-active species, we engineer highly concentrated, low viscosity liquids composed almost entirely of redox-active molecules. Using quinones as a model system, we discover a ternary benzoquinone eutectic mixture and a binary naphthoquinone eutectic mixture which have theoretical redox-active electron concentrations of 16.8 and 8.8 M e–, respectively. We investigate compatibility with protic supporting electrolytes and quantify ionic conductivity and viscosity of quinone eutectic electrolytes across multiple states of charge. A binary naphthoquinone eutectic electrolyte with a protic ionic liquid supporting electrolyte (7.1 M e–, theoretical volumetric capacity 188 Ah L–1) achieves a volumetric capacity of 49 Ah L–1 in symmetric static cell cycling. These preliminary results suggest that entropy-driven eutectic mixing is a promising strategy for developing high-energy density flow battery electrolytes.

Purchased from AmBeed: ; ; ; ; ; ; ;

Berg, Kaja ; Hegde, Pooja ; Pujari, Venugopal ; Brinkmann, Marzena ; Wilkins, David Z. ; Parish, Tanya , et al.

Abstract: The electron transport chain (ETC) in the cell membrane consists of a series of redox complexes that transfer electrons from electron donors to acceptors and couples this electron transfer with the transfer of protons (H+) across a membrane. This process generates proton motive force which is used to produce ATP and a myriad of other functions and is essential for the long-term survival of Mycobacterium tuberculosis (Mtb), the causative organism of tuberculosis (TB), under the hypoxic conditions present within infected granulomas. Menaquinone (MK), an important carrier molecule within the mycobacterial ETC, is synthesized de novo by a cluster of enzymes known as the classic/canonical MK biosynthetic pathway. MenA (1,4-dihydroxy-2-naphthoate prenyltransferase), the antepenultimate enzyme in this pathway, is a verified target for TB therapy. In this study, we explored structure-activity relationships of a previously discovered MenA inhibitor scaffold, seeking to improve potency and drug disposition properties. Focusing our campaign upon three molecular regions, we identified two novel inhibitors with potent activity against MenA and Mtb (IC50 = 13-22 μM, GIC50 = 8-10 μM). These analogs also displayed substantially improved pharmacokinetic parameters and potent synergy with other ETC-targeting agents, achieving nearly complete sterilization of Mtb in combination therapy within two weeks in vivo. These new inhibitors of MK biosynthesis present a promising new strategy to curb the continued spread of TB.

Keywords: 1,4-dihydroxy-2-naphthoate prenyltransferase ; MenA ; MenA inhibitors ; Menaquinone ; Mtb ; Mycobacterium tuberculosis ; Piperidine derivatives ; SAR

Alternative Products

Product Details of Imidazole

CAS No. :288-32-4
Formula : C3H4N2
M.W : 68.08
SMILES Code : C1=NC=CN1
Synonyms :
1,3-Diaza-2,4-cyclopentadiene; Glyoxaline
MDL No. :MFCD00005183
InChI Key :RAXXELZNTBOGNW-UHFFFAOYSA-N
Pubchem ID :795

Safety of Imidazole

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314-H360
Precautionary Statements:P280-P301+P330+P331-P305+P351+P338-P310-P303+P361+P353
Class:8
UN#:3263
Packing Group:

Isoform Comparison

Biological Activity

Description
Imidazole, a molecule with a highly polar, planar five-membered ring structure, is commonly used as a corrosion inhibitor and its derivatives exhibit antimicrobial, anti-inflammatory, and antitumor properties[1][2].

In Vitro:

Cell Line
Concentration Treated Time Description References
synovial fibroblasts 1 μM 26 hours Evaluate the effect of IKE on ferroptosis in synovial fibroblasts, results showed IKE induced cell death and lipid peroxidation Nat Commun. 2022 Feb 3;13(1):676

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
DBA/1 mice Collagen-induced arthritis (CIA) model Intraperitoneal injection 40 mg/kg Daily for 22 days Evaluate the effect of IKE on arthritis in CIA model mice, results showed IKE attenuated joint inflammation and destruction Nat Commun. 2022 Feb 3;13(1):676

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

14.69mL

2.94mL

1.47mL

73.44mL

14.69mL

7.34mL

146.89mL

29.38mL

14.69mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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