100751-63-1Relevant academic research and scientific papers
Exploring the Effect of Aliphatic Substituents on Aryl Cyano Amides on Enhancement of Fluorescence upon Binding to Amyloid-β Aggregates
Ehrlich, Rachel S.,Shiao, Alexander L.,Li, Meihan,Teppang, Kristine L.,Jeoung, Kun Yong,Theodorakis, Emmanuel A.,Yang, Jerry
, p. 2946 - 2952 (2021)
The self-assembly of amyloid-β (Aβ) peptides into amyloid aggregates is a pathological hallmark of Alzheimer's Disease. We previously reported a fluorescent Aryl Cyano Amide (ARCAM) probe that exhibits an increase in fluorescence emission upon binding to Aβ aggregates in solution and in neuronal tissue. Here, we investigate the effect of introducing small aliphatic substituents on the spectroscopic properties of ARCAM both free in solution and when bound to aggregated Aβ. We found that introducing substituents designed to hinder the rotation of bonds between the electron donor and acceptor on these fluorophores can affect the overall brightness of fluorescence emission of the probes in amyloid-free solutions, but the relative fluorescence enhancement of these probes in amyloid-containing solutions is dependent on the location of the substituents on the ARCAM scaffold. We also observed the capability to tune the excitation or emission wavelength of these probes by introducing electron-donating or -withdrawing substituents that putatively affect either the energy required for photoexcitation or the stability of the photoexcited state. These studies reveal new design principles for developing ARCAM-based fluorescent Aβ-binding probes with an enhanced fluorescence signal compared to background and tunable spectroscopic properties, which may lead to improved chemical tools for aiding in the diagnosis of amyloid-associated neurodegenerative diseases.
Diarylethene based fluorescent switchable probes for the detection of amyloid-β pathology in Alzheimer's disease
Lv, Guanglei,Cui, Baiping,Lan, Haichuang,Wen, Ying,Sun, Anyang,Yi, Tao
, p. 125 - 128 (2015)
Two fluorescent switchable diarylethene derivatives which exhibit high affinity for amyloid-β aggregates with the increase of fluorescence intensity were reported. Moreover, the probes show excellent photochromic and anti-photobleaching properties both in vitro and in vivo. This journal is
A dicyanoisophorone-based, near-infrared, lysosome-targeting pH sensor with an extremely large Stokes shift
Cai, Chunhui,Shen, Wei,Wang, Lei,Yi, Wenjun,Yu, Shian,Zhu, Qing,Zhu, Shen
, (2020)
Intracellular pH plays an important role in various biological processes; abnormal pH changes in the intracellular compartment leads to the production of free radicals, the disruption of membrane contractility, inappropriate apoptosis, and necrosis, resulting in serious illness. Although fluorescent probes have widely been used to detect pH levels owing to their high sensitivity and specificity, there is still a demand for near-infrared (NIR) fluorescent probes with high Stokes shift. Here, a NIR fluorescent probe, PipDC, comprising N-ethyl piperazine (response unit) and naphthyl dicyanoisophorone (fluorophore), was designed for pH sensing. The probe has an extremely large Stokes shift (290 nm), and its fluorescence intensity at 730 nm sharply increases when the environment changes from basic to acidic owing to the protonation of piperazine, which results in the quenching of the photoinduced electron transfer effect. It exhibited a specific response to acidic microenvironments regardless of other interfering substances. In addition, PipDC operates well in the lysosome environment in living cells and displays an off-on fluorescence response with pH alterations. Together, these results suggest that PipDC is a promising fluorescent probe for intracellular pH sensing.
Design, synthesis, and characterization of 6-[(trimethyl)silylethynyl]naphthalene-2-ethene: A new precursor for the preparation of high-refractive-index organic materials
Hannu-Kuure, Milja,K?rkk?inen, Ari,Legrand, Sacha
, (2020)
A new polymerizable naphthalene derivative has been designed, prepared, and characterized by 1H, 13C NMR, and MS. The new monomer synthesis has successfully been accomplished from a cheap commercially available raw material, in only four steps with good yields. The four steps can be easily scaled up for manufacturing purposes. It is anticipated that the new precursor can be very useful in the preparation of valuable materials with high refractive index for numerous opto-electronic applications.
Aminonaphthalene 2-cyanoacrylate (ANCA) probes fluorescently discriminate between amyloid-β and prion plaques in brain
Cao, Kevin,Dakanali, Marianna,Chang, Willy M.,Theodorakis, Emmanuel A.,Yang, Jerry,Farahi, Mona,Sigurdson, Christina J.
, p. 17338 - 17341,4 (2012)
A major challenge for diagnosing and monitoring the progression of amyloid-based diseases is the capability to distinguish between amyloid deposits that are associated with related, but distinctly different, diseases. Here, we demonstrate that aminonaphthalenyl 2-cyanoacrylate-based probes can fluorescently discriminate between different types of amyloid deposits in brain. The discriminating capability of these molecular rotors is due to the stabilization of the ground versus excited states of these probes as a function of the polarity of their microenvironment (i.e., within the binding pocket on the amyloid). This property makes it possible, for the first time, to estimate the inherent static relative permittivity (ε0) of the binding pocket of each amyloid within tissue. The capability to selectively follow the deposition of specific amyloids in tissue may provide important information for therapeutic development that is not readily accessible from currently available technology.
Method to discriminate amyloids using fluorescent probes
Teppang, Kristine L.,Ehrlich, Rachel S.,Yang, Jerry
, p. 91 - 114 (2020)
The aggregation of misfolded proteins into amyloids is a common characteristic of many neurodegenerative and non-neurologic diseases. Fluorescent amyloid-targeting probes that discriminate amyloids based on differences in protein composition can provide rapid information to aid in disease diagnosis. In this chapter, we present protocols for the synthesis and use of ANCA-11 as an environmentally-sensitive amyloid-targeting probe that can fluorescently discriminate between amyloids with different disease origin. We also present a protocol for preparing amyloid samples of synthetic Amyloid-β(1-42), as problems with amyloid preparations can be a large driver of time and cost for research. The methods presented here can be generalized for evaluation of other amyloid-targeting fluorescent probes with different aggregates of amyloidogenic proteins in solution or in tissue.
Comprehensive structure-activity-relationship of azaindoles as highly potent FLT3 inhibitors
Grimm, Sebastian H.,Gagestein, Berend,Keijzer, Jordi F.,Liu, Nora,Wijdeven, Ruud H.,Lenselink, Eelke B.,Tuin, Adriaan W.,van den Nieuwendijk, Adrianus M.C.H.,van Westen, Gerard J.P.,van Boeckel, Constant A.A.,Overkleeft, Herman S.,Neefjes, Jacques,van der Stelt, Mario
, p. 692 - 699 (2019)
Acute myeloid leukemia (AML) is characterized by fast progression and low survival rates, in which Fms-like tyrosine kinase 3 (FLT3) receptor mutations have been identified as a driver mutation in cancer progression in a subgroup of AML patients. Clinical trials have shown emergence of drug resistant mutants, emphasizing the ongoing need for new chemical matter to enable the treatment of this disease. Here, we present the discovery and topological structure-activity relationship (SAR) study of analogs of isoquinolinesulfonamide H-89, a well-known PKA inhibitor, as FLT3 inhibitors. Surprisingly, we found that the SAR was not consistent with the observed binding mode of H-89 in PKA. Matched molecular pair analysis resulted in the identification of highly active sub-nanomolar azaindoles as novel FLT3-inhibitors. Structure based modelling using the FLT3 crystal structure suggested an alternative, flipped binding orientation of the new inhibitors.
Synthesis of mono- and bibrachial naphthalene-based macrocycles with pyrene or ferrocene units for anion detection
Granzhan, Anton,Teulade-Fichou, Marie-Paule
, p. 1349 - 1360 (2009)
Three bibrachial cyclobisintercaland-type macrocycles with a 2,6-naphthylene scaffold and pyrene, ferrocene, or primary amino groups in side chains were synthesized by a [2+2]-cyclocondensation of functionalized diethylenetriamine derivatives with naphthalene-2,6-dialdehyde, whereas their monobrachial counterparts were prepared by a [1+1]-cyclocondensation of polyamines with a corresponding dialdehyde building block. The pyrene-functionalized macrocycles are able to bind orthophthalate and terephthalate anions in aqueous medium, as monitored by the changes in their fluorescence (excimer or monomer) properties.
Photoactuators based on the dynamic molecular crystals of naphthalene acrylic acids driven by stereospecific [2+2] cycloaddition reactions
Liu, Jiaxi,Ye, Kaiqi,Shen, Yanbing,Peng, Jiang,Sun, Jingbo,Lu, Ran
, p. 3165 - 3175 (2020)
The photomechanical effects of the dynamic molecular crystals of halogen-substituted naphthalene acrylic acids (1FNaAA, 1ClNaAA, 1BrNaAA, 1INaAA and 6BrNaAA) have been investigated. Upon UV irradiation, the needle-like crystal of 1FNaAA curls away from the light source, while the slice-like crystal of 6BrNaAA bends towards the light source. Moreover, the light-induced bending, flipping and bursting are observed for the elongated needle-like crystals of 1FNaAA, and the slice-like crystals of 1ClNaAA and 1BrNaAA show bending, cracking, coiling, rotating and twisting triggered by 365 nm light. It is found that stereospecific [2+2] cycloaddition reactions take place in the crystals to afford one stereoisomer of β-type cyclobutanes, since 1FNaAA, 1ClNaAA, 1BrNaAA and 6BrNaAA pack in a head-to-head mode, which satisfies the Schmidt's topo-photochemical criteria. The strain can be generated and accumulated during the photodimerization, and the release of the strain leads to the photomechanical effects. This provides new clues for the development of photomechanical molecular crystals based on acrylic acids bearing halogen-substituted aromatic units.
An expedient and multikilogram synthesis of a naphthalenoid H3 antagonist
Pu, Yu-Ming,Ku, Yi-Yin,Grieme, Timothy,Black, Lawrence A.,Bhatia, Ashok V.,Cowart, Marion
, p. 1004 - 1009 (2007)
A facile and scaleable synthesis of potent and selective histamine H3 receptor antagonist 1 is described, starting from commercially available 6-bromo-naphthalene-2-carboxylic acid methyl ester 3a. The key intermediate, 2-(6-bromonaphthalen-2-yl)ethanol 5 was prepared in good yield (78%) and purity (99%) via a one-carbon homologation of 3a. The coupling of 5 with pyridazinone 12 was accomplished effectively by a copper-catalyzed cross-coupling reaction. Activation of the hydroxyl group of 4, followed by displacement reaction with 2(R)-methylpyrrolidine 13, afforded the free base of 1, which was subsequently converted to its corresponding salt The new process consisted of eight chemical steps and one salt formation step and required no Chromatographic purification throughout the synthesis. It has been successfully implemented on pilot plant scale to prepare over 10 kg quantities of the target compound 1 in 43% overall yield in high purity (99%) and with the desired physical properties.
