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AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select... more
AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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Introduction: Intravesical therapy is critical in management of high-risk non-muscle invasive bladder cancer. The most effective intravesical therapy, BCG, has an ongoing shortage, while other second line therapies are not very effective,... more
Introduction: Intravesical therapy is critical in management of high-risk non-muscle invasive bladder cancer. The most effective intravesical therapy, BCG, has an ongoing shortage, while other second line therapies are not very effective, leaving radical cystectomy (RC) as the most effective option for cancer control. However, RC is a morbid, life-altering, and expensive procedure. Unfortunately, high-grade superficial disease is associated with cancer-specific mortality in 1/3 of the patients. Improved second line therapies or development of a BCG alternative would increase the rate of bladder preservation and survival, especially in light of the recurrent BCG shortages which have plagued bladder cancer patients. We earlier demonstrated that our first-generation imidazolium compounds are effective exfoliants that induce apoptosis via mitochondrial pathway and had potential to be used as intravesical therapy for bladder cancer. In this study, we developed and investigated second generation imidazolium compounds that have selective toxicity towards tumor tissues. We also investigated the mitochondrial target(s) of these imidazolium compounds. Methods: Second generation imidazolium compounds were screened for their toxicity against various bladder cancer cell lines using CellTiter-Glo and colony forming assay. Apoptosis induction was confirmed using western blot and propidium-iodide incorporation analysis. In vitro toxicity comparison between BBN-tumor organoids and normal organoids was performed using confocal microscopy. In vivo toxicity of these compounds was studied in normal mice. For candidate target identification, mitochondria from cells grown in SILAC heavy/light media were treated with biotinylated imidazolium compound or a mixture of biotinylated compound plus TPP1 (a first-generation imidazolium compound). Lysates were subjected to streptavidin pull down followed by LC-MS/MS proteomics analysis. Shortlisted target candidates were knocked down using siRNA followed by imidazolium treatment to assess their candidacy as the imidazolium target. Results: All second-generation imidazolium compounds had significantly higher toxicity to bladder cancer cell lines compared to first generation compounds. Compounds IS154 and IS155 were shown to be cancer selective. These two compounds showed no change in histopathology of murine bladder urothelium 24 h after intravesical instillation. Proteomics data from SILAC experiments prioritized three possible targets of the imidazolium compounds which are currently being explored. Conclusions: Second generation imidazolium compounds are tumor-specific and highly potent compounds that are worthy of further study as an intravesical agent for the treatment of high grade superficial bladder cancer. Citation Format: Uttam Satyal, David Weader, Henkel Valentine, Michael Stromyer, Wiley J. Youngs, Philip H. Abbosh. Second generation imidazolium compounds as tumor-specific intravesical therapeutic agents for non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4058.
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The title compounds are prepared by reaction of silicon and carbon in either a Pr/Co or a Nd/Co eutectic flux (alumina crucible, 950 °C, 12 h and 850 °C for 48 h).
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The reaction of 1,2-bis(tert-butyldimethylsiloxy)-3,4-bis(3-ethynylthiophene-yl)benzene (4) with Pt(P(Ph)3)2Cl2 and tetrabutylammonium fluoride produces a novel platinum catecholate complex.
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The combination of state-of-the-art polymerization chemistries, post-polymerization chemical modifications, supramolecular assembly processes and further transformations is allowing for the design of highly well-defined polymer... more
The combination of state-of-the-art polymerization chemistries, post-polymerization chemical modifications, supramolecular assembly processes and further transformations is allowing for the design of highly well-defined polymer nanoparticles that are demonstrating unique performance toward the effective treatment of infectious diseases. A potentially fully degradable, biocompatible diblock copolymer, polyphosphoester-block-poly(L-lactide) (PPE-b-PLLA), was prepared by one-pot sequential ring-opening polymerizations (ROPs) of two cyclic monomers: alkyne-functionalized phospholane and L-lactide. Photo-induced thiol-yne “click”-type reactions with small molecule thiols bearing carboxylic acid then afforded amphiphilic diblock copolymers with carboxylate side-chain functionalities along the PPE segment of the diblock copolymer backbone. Subsequently, well-defined (1) spherical micelles with negative surface charges were prepared by direct dissolution of the anionic diblock copolymers (aPPE-b-PLLA) in aqueous solution, and (2) shell crosslinked knedel-like (SCK) nanoparticles were prepared by crosslinking of hydrophilic shell of the micelles, as confirmed by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential. The Ag-loading capacities of the anionic micelles and SCKs from aPPE-b-PLLA were determined with three different types of Ag-containing molecules, silver acetate (AgOAc) and silver carbene complexes (SCC22 and SCC10). Similarly, Ag-release kinetics of the Ag-loaded nanoparticles, using dialysis cassettes in nanopure water, was studied. We are currently working on the study of (1) degradation capability of micelles and SCKs of PPE-b-PLLA system under hydrolytic or enzymatic degradation, (2) conjugation with target-specific proteins such as FimHA to evaluate their ability to perform as target delivery carriers, and (3) determination of their in vitro and in vivo efficacies against bacteria
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Structure cristalline de Rh 2 H 2 (O 2 CO)(PhC≡CPh)(P(i-Pr) 3 ) 3 : monoclinique de groupe C 24 5 -P2 1 /c avec a=17,158, b=23,916, c=11,255 A, β=103,3°, Z=4
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Research Interests: Microbiology, Medical Microbiology, Biology, Nanoparticles, Fungi, and 15 moreMedicine, Humans, Bacteria, Methane, Antimicrobial chemotherapy, Antimicrobial, Microbial Sensitivity Tests, Bacterial infections, Pseudomonas Aeruginosa, Acinetobacter baumannii, Microbial Viability, Pathogenic Bacteria, Klebsiella pneumoniae, Mycoses, and Pharmacology and pharmaceutical sciences
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... Sir: In connection with the development of an enantios-elective synthesis of naphthyridinomycin (1) and quino-carcin (2),14 we recently reported a strategy for assembly of the 3,8-diazabicyclo[ 3.2.l]octane moiety of these alka ...... more
... Sir: In connection with the development of an enantios-elective synthesis of naphthyridinomycin (1) and quino-carcin (2),14 we recently reported a strategy for assembly of the 3,8-diazabicyclo[ 3.2.l]octane moiety of these alka ... Fukuyama, T.; Li, L.; Laird, A. A,; Frank, RK Ibid. ...
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The synthesis and structural characterization of cis-(2,6-Mes2C6H3(H)2Si)Pt(H)(PPr3)2 (1), a mono(silyl)platinum(II) complex, are described.
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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full... more
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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Robustaflavone, a naturally occurring compound, is an inhibitor of hepatitis B virus replication in vitro. Robustaflavone is a biflavanoid composed of two units of apigenin (5,7,4‘-trihydroxyflavone) joined via a biaryl linkage between... more
Robustaflavone, a naturally occurring compound, is an inhibitor of hepatitis B virus replication in vitro. Robustaflavone is a biflavanoid composed of two units of apigenin (5,7,4‘-trihydroxyflavone) joined via a biaryl linkage between the 6-position of one unit and the 3‘-position of the other (I6,II3‘-biapigenin). The natural material was isolated from the seed-kernels of Rhus succedanea. To provide ready access to sufficient quantities of material for continued biological studies, as well as to provide a general route for the preparation of structural analogues, a total synthesis of robustaflavone was pursued. The total synthesis was approached by constructing apigenin ethers containing functionalities at the 6- and 3‘-positions which could be cross-coupled using transition metal catalysis. Key steps of the synthesis included development of a regioselective iodination of an apigenin derivative at the 6-position. Also key was the formation of an apigenin 3‘-boronate using a palladium-catalyzed exchange ...
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The oxidative addition reaction of (Et3P)3IrCl with H3Si(C6H3-Mes2-2,6) (Mes=2,4,6-trimethylphenyl) affords the sterically hindered iridium(III)–silyl complex (Et3P)3(H)2Ir[Si(H)Cl(C6H3-Mes2-2,6)] (1) via a H/Cl exchange reaction at... more
The oxidative addition reaction of (Et3P)3IrCl with H3Si(C6H3-Mes2-2,6) (Mes=2,4,6-trimethylphenyl) affords the sterically hindered iridium(III)–silyl complex (Et3P)3(H)2Ir[Si(H)Cl(C6H3-Mes2-2,6)] (1) via a H/Cl exchange reaction at silicon. Complex 1 is characterized by 1H-, 13C-, 31P-, and 29Si-NMR and IR spectroscopy. The solid state structure of 1 is determined by X-ray crystallography. Complex 1 undergoes a halide abstraction reaction with LiB(C6F5)4(OEt2) to afford the cationic iridium(III)–silylene complex [(Et3P)3(H)2IrSi(H)(C6H3-Mes2-2,6)][B(C6F5)4] (4). Complex 4 is characterized by 1H-, 13C-, 31P-, and 29Si-NMR spectroscopy.
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The synthesis of a dicationic imidazolium-linked cyclophane and a dimeric silver-N-heterocyclic carbene complex, that is the first silver complex with a N-heterocyclic carbene ligand involved in a pi-bonding interaction, is reported.
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The synthesis and spectroscopic characterization of the imidazolium-linked cyclophanes [1][PF6]2 and [2][PF6]2 are described. Cyclophane [1][PF6]2 contains two imidazolium rings bridged by a 2,6-bis(methyl)-pyridine unit and a... more
The synthesis and spectroscopic characterization of the imidazolium-linked cyclophanes [1][PF6]2 and [2][PF6]2 are described. Cyclophane [1][PF6]2 contains two imidazolium rings bridged by a 2,6-bis(methyl)-pyridine unit and a 2,5-bis(methyl)-pyrrole unit. Cyclophane [2][PF6]2 contains two imidazolium rings bridged by two 2,5-bis(methyl)-pyrrole units. Cyclophanes [1][PF6]2 and [2][PF6]2 have been structurally characterized by X-ray crystallography.
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Research Interests: Materials Science, Chemistry, Kinetics, Nanoparticle, Nanoparticles, and 13 moreMedicine, Multidisciplinary, Polymer, Silver, Escherichia coli, Staphylococcus aureus, Drug Design, Antimicrobial, Anti-Bacterial Agents, Microbial Sensitivity Tests, Silver Nanoparticle, Organophosphates, and Polyesters
The synthesis of the tetranuclear Ag44+ cluster stabilized by a N-heterocyclic carbene macrocycle (3)[PF6]4. Decomposition of the tetranuclear cluster (3)[PF6]4 in light forms the dimeric species (2)[PF6]2. In situ synthesis of the... more
The synthesis of the tetranuclear Ag44+ cluster stabilized by a N-heterocyclic carbene macrocycle (3)[PF6]4. Decomposition of the tetranuclear cluster (3)[PF6]4 in light forms the dimeric species (2)[PF6]2. In situ synthesis of the dimeric silver N-hetrocyclic carbene complex (2)[Br]2 in water.