1207-72-3Relevant academic research and scientific papers
Design and synthesis of new theranostic agents for near-infrared imaging of β-amyloid plaques and inhibition of β-amyloid aggregation in Alzheimer's disease
Dao, Pascal,Ye, Feifei,Du, Zhi Yun,Chen, Qian,Zhang, Kun,Dong, Chang Zhi,Meunier, Bernard,Chen, Huixiong
, p. 130 - 140 (2017)
The presence of amyloid plaques predisposes clinical symptoms of cognitive impairment, which occurs much earlier than other clinical symptoms and plays a crucial role in the neuropathology of AD. Thus, developing probes for Aβ species imaging could be used for early diagnosis of AD, and blocking the initial steps of Aβ aggregation with small molecules has emerged as a valid disease-modifying therapy for Aβ. Herein, we report the design, synthesis and evaluation of a series of new theranostic agents, which can simultaneously perform near infra-red imaging of Aβ plaques, prevent self-aggregation of Aβ monomer, disaggregate preformed Aβ fibrils and play a protective effect on the toxicity of human neuroblastoma cells (SHSY5Y) induced by Aβ1–42. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Importantly, these probes are found to have a high binding affinity toward Aβ aggregates, to exhibit a large fluorescence enhancement upon interaction with Aβ aggregates accompanied by a blueshift in the emission spectra of 20–40 nm and to show an excellent targeting ability for Aβ plaques in slices of brain and eye containing retina tissue from double transgenic mice. These molecules show a promising potential as theranostic agents for the diagnosis and therapy of AD.
Alkyl length dependent reversible mechanofluorochromism of phenothiazine derivatives functionalized with formyl group
Jia, Junhui,Wu, Yuying
, p. 537 - 543 (2017)
A series of D-A typed phenothiazine derivatives functionalized by formyl group (PCAn, n = 1, 2, 4 and 6) with different lengths of N-alkyl chains have been designed and synthesized to systematically investigate the effect of chain length on their solid-state fluorescence properties. The results showed that these compounds emitted strong fluorescence in solutions and solid states with 52%, 42%, 49% and 45% solid-state absolute fluorescence quantum yield (ΦF), respectively. Their emission wavelengths were strongly affected by solvent polarity, indicating intramolecular charge transfer (ICT) transitions. Interestingly, PCAn solids exhibit not only naked-eye visible and reversible mechanochromic behavior, but chain length-dependent emission properties. PCA1 shows smaller fluorescence spectrum shifts (22 nm) under mechanical force stimuli. Homologs with longer alkyl chains exhibit similar mechanochromic behaviors but larger fluorescence contrasts after grinding except for PCA6. Moreover, the fluorescence emission of ground solid PCA1 and PCA4 can recover at room temperature, PCA2 need high temperatures for fluorescence to be restored, and XRD and DSC revealed that the transformation between crystalline and amorphous states upon various external stimuli was responsible for the MFC behavior. This work demonstrates the feasibility of tuning the solid-state optical properties of fluorescent organic compounds by combining the simple alteration of chemical structure and the physical change of aggregate morphology under external stimuli.
Selective oxidaton methods for preparation of N-alkylphenothiazine sulfoxides and sulfones
Tosa, Monica,Paizs, Csaba,Majdik, Cornelia,Poppe, Laszlo,Kolonits, Pal,Silberg, Ioan A.,Novak, Lajos,Irimie, Florin-Dan
, p. 277 - 282 (2001)
Efficient and selective oxidation methods for preparation of N-alkylphenothiazine sulfoxides 2a-h and sulfones 3a-h starting from N-alkylphenothiazines 1a-h are described.
Molecular hybridization approach for phenothiazine incorporated 1,2,3-triazole hybrids as promising antimicrobial agents: Design, synthesis, molecular docking and in silico ADME studies
Reddyrajula, Rajkumar,Dalimba, Udayakumar,Madan Kumar
, p. 263 - 282 (2019)
The objective of the current study is to synthesize a library consisting of four sets of phenothiazine incorporated 1,2,3-triazole compounds using molecular hybridization approach. In total, 36 new hybrid molecules were synthesized and screened for in vitro growth inhibition activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Among the tested compounds, nineteen compounds exhibited significant activity with MIC value 1.6 μg/mL, which is twofold higher than the MIC value of standard first-line TB drug Pyrazinamide. In addition, all these compounds are proved to be non-toxic (with selective index > 40) against VERO cell lines. However, these compounds did not inhibit significantly the growth of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains: the activity profile is similar to that observed for standard anti-TB drugs (isoniazid and pyrazinamide), indicating the specificity of these compounds towards the Mycobacterium tuberculosis strain. Also, we report the molecular docking studies against two target enzymes (Inh A and CYP121) to further validate the antitubercular potency of these molecules. Furthermore, prediction of in silico-ADME and pharmacokinetic parameters indicated that these compounds have good oral bioavailability. The results suggest that these phenothiazine incorporated 1,2,3-triazole compounds are a promising class of molecular entities for the development of new antitubercular leads.
Trans -A2B-corrole bearing 2,3-di(2-pyridyl)quinoxaline (DPQ)/phenothiazine moieties: Synthesis, characterization, electrochemistry and photophysics
Kandhadi, Jaipal,Yan, Wei-Cong,Cheng, Fan,Wang, Hui,Liu, Hai-Yang
, p. 9987 - 9999 (2018)
Two novel donor-acceptor systems (F10C-PTZ and F10C-DPQ) were designed and synthesized, in which corrole is an acceptor and either phenothiazine (PTZ) or 2,3-di(2-pyridyl)quinoxaline (DPQ) is an energy/electron donor. These dyads represent some of the few examples of photostable corrole dyads reported in the literature, but the first example of 2,3-di(2-pyridyl)quinoxaline (DPQ) containing meso substituted corrole (F10C-DPQ) also directly connected PTZ to the meso position of corrole (F10C-PTZ). Both the dyads were characterized by high-resolution mass spectrometry (HR-MS), NMR (1H, 13C, 19F) spectroscopy, UV-Vis spectroscopy, steady state fluorescence, time-resolved fluorescence (TCSPC, MCP-PMT), electrochemical methods (CV, DPV) as well as theoretical calculations (DFT, TD-DFT). From absorption and electrochemical studies it is evident that there exist minimum π-π interactions between two hetero chromophoric units in the dyads. The steady state fluorescence studies indicate that an efficient quenching of emission corresponding to the PTZ unit in the F10C-PTZ dyad is attributed to the singlet-singlet energy transfer from PTZ to corrole. In addition to the spectral overlap, excitation spectra provided additional evidence for intramolecular energy transfer. Whereas in the F10C-DPQ dyad, a reductive electron transfer, from the ground state of DPQ to the excited state of corrole, was observed. The negative free energy (ΔG) for charge separation, anodic shift of reduction potential of corrole and the frontier molecular orbital (LUMO) location provide addition support for charge transfer. The solvent dependent rate of an energy and electron transfer was discussed.
Development of Phenothiazine-Based Theranostic Compounds That Act Both as Inhibitors of β-Amyloid Aggregation and as Imaging Probes for Amyloid Plaques in Alzheimer's Disease
Dao, Pascal,Ye, Feifei,Liu, Yan,Du, Zhi Yun,Zhang, Kun,Dong, Chang Zhi,Meunier, Bernard,Chen, Huixiong
, p. 798 - 806 (2017)
Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates (Kd = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a promising potential as theranostic agents for the diagnosis and therapy of AD.
A turn-on fluorescent BOPHY probe for Cu2+ ion detection
He, Chunhua,Zhou, Huipeng,Yang, Na,Niu, Niu,Hussain, Ejaz,Li, Yongxin,Yu, Cong
, p. 2520 - 2525 (2018)
A new fluorine-boron compound BOPHY-PTZ was designed and synthesized. The fluorescent dye was used as a highly sensitive probe for Cu2+ ion detection. The mechanism of detection involved Cu2+ ion oxidation of the phenothiazine (PTZ) moiety and blocked the intramolecular charge transfer (ICT) process from the electron-donating PTZ moiety to the electron-accepting BOPHY moiety. BOPHY-PTZ showed a weak fluorescence in solution. However, it displayed a strong fluorescence signal enhancement upon the addition of Cu2+ ions, and 1.0 nM concentration of Cu2+ can be clearly detected. The assay is simple, sensitive and convenient, and it exhibits excellent selectivity for Cu2+ ions over the other metal ions. The BOPHY-PTZ probe could be used for Cu2+ ion detection in practical samples and for environmental monitoring related applications.
Tuning the coordination properties of phenothiazine by regioselective introduction of diphenylphosphanyl groups
Filip,Gl,Lupan,Perde-Schrepler,L?nnecke,Surducan,Gin,Hey-Hawkins,Silaghi-Dumitrescu
, p. 615 - 629 (2014)
The palladium and platinum complexes of the newly synthesized 1-(diphenylphosphino)-10-methyl-10H-phenothiazine (1) and the previously reported 3-(diphenylphosphino)-10-alkyl-10H-phenothiazine [alkyl = Me (2), Et (3)] and 4-(diphenylphosphino)-10-ethyl-10H-phenothiazine (4) were prepared. Density functional calculations were carried out to explain the electronic properties of compounds 1, 3 and 4. Compounds 1, 3 and 4 can interact with DNA, as was observed in agarose gel electrophoresis experiments. In addition, the cytotoxicity of the platinum complexes of ligands 2 and 4 towards breast, colorectal and hepatocarcinoma cell lines was studied. This journal is
Photoinduced Electron Transfer from N-Alkylphenothiazines to Interface Water of Sodium Dodecyl Sulfate Micelles as a Function of Poly(ethylene oxide) Interaction with the Interface
Kang, Young Soo,Kevan, Larry
, p. 2478 - 2481 (1994)
Photoinduced electron transfer from N-alkylphenothiazines (PCn, n = 1, 3, 6, 12, and 16) solubilized in sodium dodecyl sulfate (SDS) micelle interacting with poly(ethylene oxide) (PEO) to interface D2O as an electron acceptor is studied with electron spin resonance (ESR) and electron spin echo modulation.The photoproduced radicals are identified as the N-alkylphenothiazine cation radical and the surfactant alkyl chain radical of SDS.The total photoyield decreased from PC1 to PC3 and then increased to PC16.The photoyields increased monotonically with increasing PEO concentration.The photoyields are correlated with the deuterium modulation depth of PCn+ with D2O at the micelle interface as a function of the alkyl chain length of PCn and the concentration of PEO since the modulation depth measures relative changes in the interaction distance between the phenothiazine moiety and interface D2O.The photoyield and deuterium modulation depth trends show a good correlation which indicates that the electron transfer from phenothiazine moiety to interface water is mainly controlled by the distance between them, which is controllably varied by the alkyl chain length of phenothiazine and the intercalation of PEO into the interface region of the SDS micellar headgroup.
Benzothiazole-Phenothiazine Conjugate Based Molecular Probe for the Differential Detection of Glycated Albumin
Kumar, Ashish,Datta, Lakshmi Priya,Samanta, Sourav,Arora, Harshit,Govindaraju, Thimmaiah
, p. 222 - 230 (2021)
Glycation of albumin proteins is considered the pathophysiological hallmark of several chronic fatal disorders, including diabetes mellitus (DM) and Alzheimer's disease (AD). The optical detection of glycated albumin is a simple and cost-effective tool with diagnostic implications for DM and AD. Herein, we developed a cyano derivative of the benzothiazole-phenothiazine conjugate (TCNP) -based far-red fluorescence probe for the differential detection of glycated bovine serum albumin (BSAG) over native BSA and oxidized BSA (BSAO). The selective fluorescence enhancement of TCNP in the presence of native BSA and BSAO and significant quenching in the presence of BSAG account for the distinct interaction between the probe and different structural variants of BSA. The high photostability and differential response towards native BSA and BSAG infer that TCNP is a potential molecular tool to assess the glycation induced structural changes of albumins.
