A5067763726- Synthesis and Biological Evaluation
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Synthesis and Reactions of Organic Compounds
- Fluorine in Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Synthesis and Characterization of Heterocyclic Compounds
- Parasitic Infections and Diagnostics
- Catalytic Cross-Coupling Reactions
- Catalytic C–H Functionalization Methods
- Synthesis and biological activity
- Synthesis of heterocyclic compounds
- HIV/AIDS drug development and treatment
- Toxoplasma gondii Research Studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Organic Chemistry Cycloaddition Reactions
- Chemical Synthesis and Reactions
- Synthesis and Reactivity of Heterocycles
- DNA and Nucleic Acid Chemistry
- Chemical Reaction Mechanisms
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Organoselenium and organotellurium chemistry
- X-ray Diffraction in Crystallography
- Synthesis and Catalytic Reactions
Augusta University
2013-2021
Georgia State University
2005-2017
Fundação Oswaldo Cruz
2017
Georgia Regents Medical Center
2013-2015
Augusta University Health
2015
University of Pittsburgh
2013-2014
Washington State University
2013
John Peter Smith Hospital
2008
University of South Carolina
1996-2006
Swiss Tropical and Public Health Institute
2005
Report7 November 2017Open Access Transparent process G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and vivo Roberto Simone Department of Neurodegenerative Disease, UCL Institute Neurology, London, UK Search for more papers by this author Rubika Balendra Genetics, Evolution Environment, Healthy Ageing, University College Thomas G Moens Elisavet Preza Molecular Neuroscience, Katherine M Wilson Amanda Heslegrave Nathan S Woodling Teresa Niccoli Javier...
Dicationic 2,5-bis(4-guanidinophenyl)furans 5a−5f, 2,5-bis[4-(arylimino)aminophenyl]furans 6a−6b and 6e−6k, 2,5-bis[4-(alkylimino)aminophenyl]furans 6c−6d have been synthesized starting from 2,5-bis[tri-n-butylstannyl]furan. Thermal melting studies with poly dA•dT the duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for a number of compounds. The are highly dependent on structure significantly affected by substituents both phenyl rings 2,5-diphenylfuran nucleus...
DB289 [2,5-bis(4-amidinophenyl)furan-bis-<i>O</i>-methylamidoxime] is biotransformed to the potent antiparasitic diamidine DB75 [2,5-bis(4-amidinophenyl) furan] by sequential oxidative <i>O</i>-demethylation and reductive <i>N</i>-dehydroxylation reactions. Previous work demonstrated that reactions are catalyzed cytochrome <i>b</i><sub>5</sub>/NADH-cytochrome <i>b</i><sub>5</sub> reductase. Enzymes responsible for catalyzing pathway have not been identified. We report an in vitro metabolism...
ABSTRACT Chagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, caused by the intracellular parasite Trypanosoma cruzi . The goal of this work to investigate in vitro and vivo effects arylimidamide (AIA) DB766 against T. This exhibits strong trypanocidal activity excellent selectivity bloodstream trypomastigotes amastigotes (Y strain), giving IC 50 s (drug concentrations that reduce 50% number treated parasites) 60 25 nM, respectively. also exerts striking...
Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC(50)], <1 microM) against both Leishmania donovani axenic amastigotes and intracellular Leishmania, the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize in vitro vivo activities, pharmacokinetics, mutagenicities, toxicities two novel AIAs, DB745 DB766. They were exceptionally active...
ETS transcription factors mediate a wide array of cellular functions and are attractive targets for pharmacological control gene regulation. We report the inhibition ETS-family member PU.1 with panel novel heterocyclic diamidines. These diamidines derivatives furamidine (DB75) in which central furan has been replaced selenophene and/or one or both bridging phenyl benzimidazole. Like all proteins, binds sequence specifically to 10-bp sites by inserting recognition helix into major groove...
Direct modulation of gene expression by targeting oncogenic transcription factors is a new area research for cancer treatment. ERG, an ETS-family factor, commonly over-expressed or translocated in leukaemia and prostate carcinoma. In this work, we selected the di-(thiophene-phenyl-amidine) compound DB1255 as ERG/DNA binding inhibitor using screening test synthetic inhibitors interaction followed electrophoretic mobility shift assays (EMSA) validation. Spectrometry, footprint...
Most transcription factors were for a long time considered as undruggable targets because of the absence binding pockets direct targeting. HOXA9, implicated in acute myeloid leukemia, is one them. To date, only indirect targeting HOXA9 expression or multitarget HOX/PBX protein/protein interaction inhibitors has been developed. As an attractive alternative by inhibiting DNA binding, we selected series heterocyclic diamidines efficient competitors HOXA9/DNA through minor groove ligands on...
Fluorescence microscopy has been used to study the cellular distribution properties of a series DNA binding cationic compounds related potent antiparasitic drug furamidine (DB75). The tested bear diphenylfuran or phenylfuranbenzimidazole unfused aromatic core substituted with one two amidine imidazoline groups. synthesis five new is reported. B16 melanoma cell line was compare capacities mono-, bis-, and tetracations enter nuclei. high-resolution fluorescence pictures show that in series,...
Dicationic guanidine, N-alkylguanidine, and reversed amidine derivatives of fused ring systems (9a−d, 12a−c, 13a, 13b) have been synthesized from their corresponding bis-amines. DNA binding studies suggest that the diguanidines N-alkyl fluorenes bind in minor groove a manner similar to previously reported dicationic carbazole derivatives. The showed promising vitro activity against both Trypanosoma brucei rhodesiense Plasmodium falciparum. Promising vivo biological results were obtained for...
The aim of this study was to develop and validate a quantitative anti-signal recognition particle (SRP) autoantibody serum ELISA in patients with myositis longitudinal association disease activity.We developed using recombinant purified full-length human SRP coated on plates secondary antibody that bound IgG detect anti-SRP binding. Protein immunoprecipitation used as the gold standard for presence anti-SRP. Serum samples from three groups were analysed: SRP(+) subjects by...
The Human Genome Project as well sequencing of the genomes other organisms offers a wealth DNA targets for both therapeutic and diagnostic applications, it is important to develop additional binding motifs fully exploit potential this new information. We have recently found that an aromatic dication, DB293, with amidine-phenyl-furan-benzimidazole-amidine structure can recognize specific sequences by in minor groove dimer [Wang, L., Bailly, C., Kumar, A., Ding, D., Bajic, M., Boykin, D. W.,...
Aromatic diamidines represent a class of DNA minor groove-binding ligands that exhibit high levels antiparasitic activity. Since the chemotherapy for Chagas' disease is still an unsolved problem and previous reports on related analogues show they have activity against Trypanosoma cruzi infection both in vitro vivo, our present aim was to evaluate cellular effects three reversed amidines (DB889, DB702, DB786) one diguanidine (DB711) amastigotes bloodstream trypomastigotes T. cruzi,...
The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new more efficient treatment options are urgently needed. By employing a recently validated assay the release functional phosphoglucose isomerase (PGI) from dying parasites, activities 26 dicationic compounds (+)- (-)-erythro-enantiomers mefloquine were investigated. Initial screening was...
Neospora caninum is considered to be the main cause of bovine abortion in Europe and USA, leading considerable financial impact. Losses are caused directly by abortions or indirectly through breeding calves with impaired viability. Due lack effective chemotherapy against neosporosis, there a need develop new anti-protozoal compounds, which would either eliminate parasite avoid its transmission. In order identify compounds interest, vitro activities 41 di-cationic pentamidine derivatives were...