- F?rster Resonance Energy Transfer-Based Fluorescent Probe for the Selective Imaging of Hydroxylamine in Living Cells
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Hydroxylamine (HA) is an important product of cell metabolism and plays a significant role in many biological processes, and therefore, real-time imaging of HA is of great importance for the in-depth study of its physiological and pathological functions. However, a HA-specific fluorescent probe is currently lacking primarily because the highly selective HA-responsive site is undeveloped. To address this critical issue, we present a HA-specific FRET-based fluorescent probe (RhChr) for the selective detection of HA in living systems. Inspired by aza-Michael addition, the unsaturated system appended with an iminium ion was employed as the new HA-specific response site. In response to HA, RhChr provided a ratiometric signal output with excellent selectivity toward HA over biothiols and ammonia. We have demonstrated that RhChr could be applied for the ratiometric imaging of endogenous HA in living cells and the evaluation of xanthine oxidase (XOD) activity in living organs.
- Dong, Baoli,Tian, Minggang,Kong, Xiuqi,Song, Wenhui,Lu, Yaru,Lin, Weiying
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- Novel piperazine–chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation
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New piperazine–chalcone hybrids and related pyrazoline derivatives have been designed and synthesised as potential vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The National Cancer Institute (NCI) has selected six compounds to evaluate their antiproliferative activity in vitro against 60 human cancer cells lines. Preliminary screening of the examined compounds indicated promising anticancer activity against number of cell lines. The enzyme inhibitory activity against VEGFR-2 was evaluated and IC50 of the tested compounds ranged from 0.57 μM to 1.48 μM. The most potent derivatives Vd and Ve were subjected to further investigations. A cell cycle analysis showed that both compounds mainly arrest HCT-116 cell cycle in the G2/M phase. Annexin V-FITC apoptosis assay showed that Vd and Ve induced an approximately 18.7-fold and 21.2-fold total increase in apoptosis compared to the control. Additionally, molecular docking study was performed against VEGFR (PDB ID: 4ASD) using MOE 2015.10 software and Sorafenib as a reference ligand.
- Ahmed, Marwa F.,El-Haggar, Radwan,Santali, Eman Y.
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- Ratio-type fluorescent probe for bisulfite detection and preparation method and application thereof
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The invention discloses a preparation method and application of a ratio-type fluorescent probe for bisulfite detection. A molecular formula of the probe is C29H29N6O4, abbreviated as: CBP-N, and recognition characteristics of the probe CBP-N with small molecule substances such as metal ions, common amino acids, active oxygen, and active sulfur in a CH3CN-PBS solution are studied by a fluorescence spectrometer. The results show that the probe CBP-N has efficient and specific selectivity for bisulfite, and has relatively strong anti-interference ability, and a minimum detection limit is 18 nM. After the probe CBP-N responded to bisulfite, in a fluorescence emission spectrum, the fluorescence intensity at 549 nm is significantly enhanced, and the fluorescence intensity at 631 nm is significantly reduced, so that the ratio-type detection of bisulfite can be realized, the characteristic can overcome the interference of common factors in the environment, and the probe has relatively goodpractical application value.
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Paragraph 0025
(2020/01/03)
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- Structure-Based Optimization of Pyridoxal 5′-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis
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The pyridoxal 5′-phosphate (PLP)-dependent transaminase BioA catalyzes the second step in the biosynthesis of biotin in Mycobacterium tuberculosis (Mtb) and is an essential enzyme for bacterial survival and persistence in vivo. A promising BioA inhibitor 6 containing an N-aryl, N′-benzoylpiperazine scaffold was previously identified by target-based whole-cell screening. Here, we explore the structure-activity relationships (SAR) through the design, synthesis, and biological evaluation of a systematic series of analogues of the original hit using a structure-based drug design strategy, which was enabled by cocrystallization of several analogues with BioA. To confirm target engagement and discern analogues with off-target activity, each compound was evaluated against wild-type (WT) Mtb in biotin-free and -containing medium as well as BioA under- and overexpressing Mtb strains. Conformationally constrained derivative 36 emerged as the most potent analogue with a KD of 76 nM against BioA and a minimum inhibitory concentration of 1.7 μM (0.6 μg/mL) against Mtb in biotin-free medium.
- Liu, Feng,Dawadi, Surendra,Maize, Kimberly M.,Dai, Ran,Park, Sae Woong,Schnappinger, Dirk,Finzel, Barry C.,Aldrich, Courtney C.
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p. 5507 - 5520
(2017/07/22)
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- 1-SUBSTITUTED, 4-(SUBSTITUTED PHENOXYMETHYL)-1,2,3-TRIAZOLE COMPOUNDS WITH ANTIFUNGAL PROPERTIES AND METHODS FOR PREPARATION THEREOF
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Disclosed herein are novel antifungal compounds of Formula 1, containing 1 -substituted, 4-(substituted phenoxymethyl)-l,2,3-triazole moieties coupled to a core having triazole ring, (un)substituted phenyl ring and tertiary alcoholic functionality, and pharmaceutically acceptable salts thereof; methods for preparing these compounds; and pharmaceutical preparations containing these novel compounds for prevention and treatment of fungal infections.
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Page/Page column 33
(2014/09/16)
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- PIPERAZINE-BASED SENSITISERS
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Compounds of formula (I) {where: R1 is methyl, ethyl, cycloalkyl or optionally substituted aryl; Z is arylene or a group of formula -(CHR4)n-, where R4 is hydrogen, hydroxy or alkyl, and n is a number from 0 to 6; Y is carbonyl or a -CH2- group; Q is a residue of a mono- or poly- hydroxy compound having from I to 6 hydroxy groups; and x is a number from I to 6; and esters thereof} are useful as sensitisers for use in radiation-curable compositions.
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- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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- 1-ARYL-4-SUBSTITUTED PIPERAZINES DERIVATIVES FOR USE AS CCR1 ANTAGONISTS FOR THE TREATMENT OF INFLAMMATION AND IMMUNE DISORDERS
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Compounds are provided that act as potent antagonists of the CCR1 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR1. The compounds are generally aryl piperazine derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR1-mediated diseases, and as controls in assays for the identification of competitive CCR1 antagonists.
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- Sequential mono-N-arylation of piperazine nitrogens. Part 1: A simplified method and its application to the preparation of a key N,N'-biaryl piperazine antifungal intermediate
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A simple sequential N-arylation of piperazine without the use of a protecting group, catalyst, specialized equipment or a large excess of piperazine, and its application towards the preparation of the key differentially N,N'-biarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N'-(4-aminophenyl)piperazine, 6, is described.
- Hepperle, Michael,Eckert, Jeffrey,Gala, Dinesh
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p. 5655 - 5659
(2007/10/03)
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- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
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This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones
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This invention relates to compounds of Formula I STR1 which are useful in association with a pharmaceutical carrier as antiatherosclerotic agents. In addition, various compounds of Formula I are useful inhibitors of cell proliferation.
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- Rapid and efficient synthesis of 1-Arylpiperazines under microwave irradiation
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1-Arylpiperazines, finding wide applicability in pharmaceuticals were synthesized easily under microwave irradiation from bis(2-chloroethyl)amine hydrochloride and substituted anilines without any solvent. The reaction time was just 1-3 mins. 1-Arylpiperazines were synthesized in 53 to 73% yields. Potent serotonin ligands like Trifluoromethylphenylpiperazine (TFMPP) and 3-Chlorophenylpiperazine (mCPP) were also prepared in just 1 min and 2 mins respectively.
- Jaisinghani, Harsha G.,Khadilkar, Bhushan M.
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p. 6875 - 6876
(2007/10/03)
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- Antiatherosclerotic and antithrombotic 2-amino-6-phenyl-4H-pyran-4-ones
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This invention relates to compounds of Formula I STR1 which are useful as antiatherosclerotic agents and inhibitors of cell proliferation for the treatment of proliferative diseases. In addition, various compounds of Formula I are useful inhibitors of platelet aggregation.
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