2199-58-8Relevant articles and documents
Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox Processes
Greene, Lana E.,Godin, Robert,Cosa, Gonzalo
, p. 11327 - 11334 (2016)
We report herein the synthesis and characterization of a fluorogenic analogue of ubiquinone designed to reversibly report on redox reactions in biological systems. The analogue, H2B-Q, consists of the redox-active quinone segment found in ubiquinone, 2,3-dimethoxy-1,4-benzoquinone, coupled to a boron-dipyrromethene (BODIPY) fluorophore segment that both imparts lipophilicity in lieu of the isoprenyl tail of ubiquinone, and reports on redox changes at the quinone/quinol segment. Redox sensing is mediated by a photoinduced electron transfer intramolecular switch. In its reduced dihydroquinone form, H2B-QH2 is highly emissive in nonpolar media (quantum yields 55-66%), while once oxidized, the resulting quinone H2B-Q emission is suppressed. Cyclic voltammetry of H2B-Q shows two reversible, 1-electron reduction peaks at -1.05 V and -1.37 V (vs ferrocene) on par with those of ubiquinone. Chemical reduction of H2B-Q by NaBH4 resulted in >200 fold emission enhancement. H2B-QH2 is shown to react with peroxyl radicals, a form of reactive oxygen species (ROS) as well as to cooperatively interact with chromanol (the active segment of α-tocopherol). Kinetic analysis further shows the antioxidant reactivity of the nonfluorescent intermediate semiquinone. We anticipate that the H2B-Q/H2B-QH2 off/on reversible couple may serve as a tool to monitor chemical redox processes in real-time and in a noninvasive manner.
Halogenated BODIPY photosensitizers: Photophysical processes for generation of excited triplet state, excited singlet state and singlet oxygen
Hu, Wenbin,Liu, Jiatian,Luo, Lin,Zhang, Rui,Zhang, Xian-Fu
, (2022/02/09)
We have systematically examined the formation of singlet oxygen O2(1Δg), the excited triplet state (T1), and excited singlet state (S1) for halogenated BODIPY photosensitizers (halogen = Cl, Br, and I
BOPHY-Fullerene C60 Dyad as a Photosensitizer for Antimicrobial Photodynamic Therapy
Gonzalez Lopez, Edwin J.,Sarotti, Ariel M.,Martínez, Sol R.,Macor, Lorena P.,Durantini, Javier E.,Renfige, Melisa,Gervaldo, Miguel A.,Otero, Luis A.,Durantini, Andrés M.,Durantini, Edgardo N.,Heredia, Daniel A.
, (2022/01/08)
A novel BOPHY–fullerene C60 dyad (BP-C60) was designed as a heavy-atom-free photosensitizer (PS) with potential uses in photodynamic treatment and reactive oxygen species (ROS)-mediated applications. BP-C60 consists of a BOPHY fluorophore covalently attached to a C60 moiety through a pyrrolidine ring. The BOPHY core works as a visible-light-harvesting antenna, while the fullerene C60 subunit elicits the photodynamic action. This fluorophore–fullerene cycloadduct, obtained by a straightforward synthetic route, was fully characterized and compared with its individual counterparts. The restricted rotation around the single bond connecting the BOPHY and pyrrolidine moieties led to the formation of two atropisomers. Spectroscopic, electrochemical, and computational studies disclose an efficient photoinduced energy/electron transfer process from BOPHY to fullerene C60. Photodynamic studies indicate that BP-C60 produces ROS by both photomechanisms (type I and type II). Moreover, the dyad exhibits higher ROS production efficiency than its individual constitutional components. Preliminary screening of photodynamic inactivation on bacteria models (Staphylococcus aureus and Escherichia coli) demonstrated the ability of this dyad to be used as a heavy-atom-free PS. To the best of our knowledge, this is the first time that not only a BOPHY–fullerene C60 dyad is reported, but also that a BOPHY derivative is applied to photoinactivate microorganisms. This study lays the foundations for the development of new BOPHY-based PSs with plausible applications in the medical field.
Synthesis and study of organoselenium compound: DNA/Protein interactions, in vitro antibacterial, antioxidant, anti-inflammatory activities and anticancer activity against carcinoma cells
Dhavan, Pratik P.,Jadhav, Bhaskar L.,Manjare, Sudesh T.,Shelar, Divyesh S.,Singh, Pinky R.,Vaidya, Shashikant P.
, (2021/07/25)
New organoselenium compound was synthesized and characterized using common spectroscopic techniques. The organoselenium compound binds to Hs-DNA through hydrophobic and hydrogen binding interactions and partial intercalation in the base pairs of DNA was observed, this was also confirmed from circular dichroism (CD). The organoselenium compound was screened for potential anti-oxidant, anti-bacterial and anti-inflammatory activities using various techniques, which demonstrated better results in comparison to standards. The agarose gel electrophoresis study suggested the protective nature of organoselenium compound against supercoiled pBR322 plasmid DNA in presence of Fenton's reagent. In addition, in vitro cytotoxicity experiments against A549 and HeLa cancer cells were performed which evidenced promising anti-cancer activities with significantly low IC50 values.
Virtual Screening Identifies Irreversible FMS-like Tyrosine Kinase 3 Inhibitors with Activity toward Resistance-Conferring Mutations
Bensinger, Dennis,Stubba, Daniel,Cremer, Anjali,Kohl, Vanessa,Wa?mer, Theresa,Stuckert, Johanna,Engemann, Victoria,Stegmaier, Kimberly,Schmitz, Katja,Schmidt, Boris
supporting information, p. 2428 - 2446 (2019/03/11)
The use of covalent irreversible binding inhibitors is an established concept for drug development. Usually, the discovery of new irreversible kinase inhibitors occurs serendipitously, showing that efficient rational approaches for the rapid discovery of new drugs are needed. Herein, we report a virtual screening strategy that led to the discovery of irreversible inhibitors of FMS-like tyrosine kinase 3 (FLT3) involved in the pathogenesis of acute myeloid leukemia. A virtual screening library was designed to target the highly conserved Cys828 residue preceding the DFG motif by modification of reported reversible inhibitors with chemically reactive groups. Prospective covalent docking allowed the identification of two lead series, resulting in a massive increase in inhibition of kinase activity and cell viability by irreversible inhibitors compared to the corresponding reversible scaffolds. Lead compound 4b (BSc5371) displays superior cytotoxicity in FLT3-dependent cell lines to compounds in recent clinical trials and overcomes drug-resistant mutations.
Synthesis and reactivity of 2-thionoester pyrroles: A route to 2-formyl pyrroles
Kim, Min Joon,Gaube, Sophie M.,Beh, Michael H. R.,Smith, Craig D.,Thompson, Alison
, p. 31773 - 31780 (2019/10/19)
2-Functionalised pyrroles exhibit considerable synthetic utility. Herein, the synthesis and reactivity of 2-thionoester (-C(S)OR) pyrroles is reported. 2-Thionoester pyrroles were synthesised using a Knorr-type approach from aliphatic starting materials. 2-Thionoester pyrroles were reduced to the corresponding 2-formyl pyrroles, or the deuterated formyl variant, in one step using RANEY nickel, thereby removing the need for the much-utilised hydrolysis/decarboxylation/formylation steps that are typically required to convert Knorr-type 2-carboxylate pyrroles into 2-formyl pyrroles. 2-Thionoester pyrroles proved tolerant of typical functional group interconversions for which the parent 2-carboxylate pyrroles have become known.
5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells
Shah, Sajita,Lee, Chaemin,Choi, Hyukjae,Gautam, Jaya,Jang, Hyeonjin,Kim, Geum Jin,Lee, Yu-Jeong,Chaudhary, Chhabi Lal,Park, Sang Won,Nam, Tae-Gyu,Kim, Jung-Ae,Jeong, Byeong-Seon
, p. 4829 - 4841 (2016/06/13)
Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib.
Preparation, spectral and thermal properties of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes with iodosubstituted 2,2′-dipyrrolylmethene
Guseva,Antina,Beresin,V'Yugin,Nuraneeva
, p. 1571 - 1579 (2013/10/22)
Complexes [ML2] of cobalt(II), nickel(II), copper(II), zinc(II), and cadmium(II) with asymmetrically substituted (E)-3-ethyl-5-[(4-iodo-3,5- dimethyl-2H-pyrrol-2-ylidene)methyl]-2,4-dimethyl-1H-pyrrole (HL) have been prepared and characterized for the first time. The spectral properties, stability in solutions and in the solid phase at elevated temperature of the complexes have been studied. The effects of complexing metal ion and the reaction medium on the spectral luminescent properties (absorptivity, quantum yield, fluorescence lifetime, and the radiation constant) and on thermal destruction of the [ML2] complexes have been discussed.
Tunable BODIPY derivatives amenable to 'click' and peptide chemistry
Hansen, Anna Mette,Sewell, Alan L.,Pedersen, Rasmus H.,Long, De-Liang,Gadegaard, Nikolaj,Marquez, Rodolfo
, p. 8527 - 8533 (2013/09/02)
Novel azido- and amino-functionalised fluorescent probes based on the BODIPY framework have been developed. The probes can be easily and cheaply synthesised, exhibit the highly desirable BODIPY fluorescent properties, and are amenable to 'click' and pepti
Synthesis and characterisation of neutral mononuclear cuprous complexes based on dipyrrin derivatives and phosphine mixed-ligands
Liu, Xiaohui,Nan, Hongmei,Sun, Wei,Zhang, Qikai,Zhan, Mingjian,Zou, Luyi,Xie, Zhiyuan,Li, Xiao,Lu, Canzhong,Cheng, Yanxiang
, p. 10199 - 10210 (2013/01/14)
Heteroleptic neutral mononuclear cuprous complexes with dipyrrin derivatives and phosphine mixed-ligands including 1,3,7,9-tetramethyldipyrrin (1), 5-phenyl-1,3,7,9-tetramethyldipyrrin (2), 2,8-dibromo-1,3,7,9- tetramethyldipyrrin (3), 1,9-dichloro-5-phen
