- Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox Processes
-
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.
- Greene, Lana E.,Godin, Robert,Cosa, Gonzalo
-
-
Read Online
- Halogenated BODIPY photosensitizers: Photophysical processes for generation of excited triplet state, excited singlet state and singlet oxygen
-
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
- Hu, Wenbin,Liu, Jiatian,Luo, Lin,Zhang, Rui,Zhang, Xian-Fu
-
-
- BOPHY-Fullerene C60 Dyad as a Photosensitizer for Antimicrobial Photodynamic Therapy
-
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.
- 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.
-
-
- Synthesis and study of organoselenium compound: DNA/Protein interactions, in vitro antibacterial, antioxidant, anti-inflammatory activities and anticancer activity against carcinoma cells
-
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.
- Dhavan, Pratik P.,Jadhav, Bhaskar L.,Manjare, Sudesh T.,Shelar, Divyesh S.,Singh, Pinky R.,Vaidya, Shashikant P.
-
-
- Synthesis and reactivity of 2-thionoester pyrroles: A route to 2-formyl pyrroles
-
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.
- Kim, Min Joon,Gaube, Sophie M.,Beh, Michael H. R.,Smith, Craig D.,Thompson, Alison
-
p. 31773 - 31780
(2019/10/19)
-
- Virtual Screening Identifies Irreversible FMS-like Tyrosine Kinase 3 Inhibitors with Activity toward Resistance-Conferring Mutations
-
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.
- 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)
-
- 5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells
-
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.
- 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)
-
- Preparation, spectral and thermal properties of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes with iodosubstituted 2,2′-dipyrrolylmethene
-
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.
- Guseva,Antina,Beresin,V'Yugin,Nuraneeva
-
p. 1571 - 1579
(2013/10/22)
-
- Tunable BODIPY derivatives amenable to 'click' and peptide chemistry
-
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
- Hansen, Anna Mette,Sewell, Alan L.,Pedersen, Rasmus H.,Long, De-Liang,Gadegaard, Nikolaj,Marquez, Rodolfo
-
p. 8527 - 8533
(2013/09/02)
-
- Synthesis and characterisation of neutral mononuclear cuprous complexes based on dipyrrin derivatives and phosphine mixed-ligands
-
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
- 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)
-
- Synthesis and spectral properties of new 3,3'-bis(dipyrrolylmethene) with acetylene spacer
-
Bis(2,4,7,9-tetramethyl-8-ethyldipyrrolylmethen-3-yl)acetylene dihydrobromide (H2L·2HBr), new bis(dipyrrolylmethene), in whose molecule dipyrrolylmethene domains were connected through 3,3'-carbon atoms of internal pyrrole nuclei by acetylene spacer, were synthesized by original procedure. The compound was characterized by element analysis, IR, 1H NMR, and electronic spectroscopy. The comparative analysis of spectral properties shows the reduction of the basicity of H2L ligand in comparison with the structural analogs, which contain internal methylene spacer. The quantum-chemical simulation showed that the rigid acetylene spacer gives linear structure to the H2L molecule in contrast to the spiral-shaped geometry of structural analogs with-CH2-spacer. Pleiades Publishing, Ltd., 2010.
- Antina,Guseva,Loginova,Semeikin,V'Yugin
-
p. 2374 - 2381
(2011/04/14)
-
- A new synthesis of symmetric boraindacene (BODIPY) dyes
-
BODIPY dyes were synthesized from pyrrole-2-carbaldehyde derivatives in high yields; this constitutes a new approach to this dye framework. The Royal Society of Chemistry.
- Wu, Liangxing,Burgess, Kevin
-
supporting information; experimental part
p. 4933 - 4935
(2009/06/06)
-
- Pyrrolotriazine inhibitors of kinases
-
The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
- -
-
Page/Page column 28
(2008/06/13)
-
- Indolinone combinatorial libraries and related products and methods for the treatment of disease
-
The present invention relates to organic molecules capable of modulating, regulating and/or inhibiting protein kinase signal transduction. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction, including cell proliferative diseases such as cancer, atherosclerosis, arthritis and restenosis and metabolic diseases such as diabetes. The present invention features indolinone compounds that potently inhibit protein kinases and related products and methods. Inhibitors specific to the FLK protein kinase can be obtained by adding chemical substituents to the 3-[(indole-3-yl)methylene]-2-indolinone, in particular at the 1' position of the indole ring. Indolinone compounds that specifically inhibit the FLK and platelet derived growth factor protein kinases can harbor a tetrahydroindole or cyclopentano-b-pyrrol moiety. Indolinone compounds that are modified with substituents, particularly at the 5 position of the oxindole ring, can effectively activate protein kinases. This invention also features novel hydrosoluble indolinone compounds that are tyrosine kinase inhibitors and related products and methods.
- -
-
-
- Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes
-
This invention describes novel 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes containing heteroaryl substituents conjugated to the fluorophore and methods for their synthesis. The heteroaryl substituted compounds (heteroaryl dyes) generally have the structure: STR1 wherein any or all of the substituents R1 -R7, but at least one of such substituents, is a heteroaryl group, including 5- or 6-member rings, singly or fused, containing one or more heteroatoms. The new dyes that have spectral properties that are significantly shifted from those of the parent alkyl-substituted dyes, usually accompanied by an increase in photostability and in some cases by an increase in the extinction coefficient relative to the alkyl-substituted dyes. The general method of synthesis includes formation of pyrromethene salt intermediates followed by cyclization with boron trifluoride in the presence of a base to give heteroaryl-substituted dipyrrometheneboron difluoride dyes.
- -
-
-
- Peripheral Mercuration of Metalloporphyrins: Novel Syntheses of Deoxophylloerythroetioporphyrin and Deoxophylloerythrin Methyl Ester
-
Zinc(II) porphyrins bearing unsubstituted β positions can be mercurated at the β position and at an adjacent meso position.Palladium / olefin reactions with the dimercurated porphyrins produce products possessing a five-membered isocyclic ring bridging the β and meso positions and resembling that found in chlorophyll derivatives.With use of this methodology, novel syntheses of deoxophylloerythroetioporphyrin (2) and deoxophylloerythrin methyl ester (3), two degradation products of chlorophyll, are described.
- Smith, Kevin M.,Langry, Kevin C.,Minnetian, Ohannes M.
-
p. 4602 - 4609
(2007/10/02)
-
