A5041250326- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Cholinesterase and Neurodegenerative Diseases
- Chemical synthesis and alkaloids
- Computational Drug Discovery Methods
- Genetic Neurodegenerative Diseases
- Phosphodiesterase function and regulation
- Insect and Pesticide Research
- Nicotinic Acetylcholine Receptors Study
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Properties of Aromatic Compounds
- Photochemistry and Electron Transfer Studies
- Educational Research and Science Teaching
- Spectroscopy and Chemometric Analyses
- Chemical Reaction Mechanisms
- Spectroscopy and Quantum Chemical Studies
- Synthesis and Catalytic Reactions
- Educational theories and practices
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Education Methods and Integration
- Nanopore and Nanochannel Transport Studies
- DNA and Biological Computing
- Statistics Education and Methodologies
- Animal health and immunology
- Free Radicals and Antioxidants
Auburn University
2025
SOM Biotech (Spain)
2016-2023
Universidad de Costa Rica
2010-2013
Universidad Nacional
2010-2013
Universitat de Barcelona
2005-2011
University of Pennsylvania
2009
University of Tennessee at Knoxville
2009
Universidad Autónoma Metropolitana
2008
Oak Ridge National Laboratory
2006-2008
Material Sciences (United States)
2006
Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase, AChE-induced self-induced β-amyloid (Aβ) aggregation, β-secretase (BACE-1) cross blood−brain barrier. The new hybrids consist a unit 6-chlorotacrine multicomponent reaction-derived pyrano[3,2-c]quinoline scaffold as the active-site peripheral-site interacting moieties, respectively, connected through an...
Abstract Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological aggregation. Native state stabilizers are promising drugs to treat Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as potent aggregation inhibitor. Tolcapone binds specifically human plasma, stabilizes the native vivo mice and humans inhibits cytotoxicity. Crystal structures of tolcapone bound wild-type V122I...
Tacripyrines (1−14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop multitarget therapeutic strategy confront AD. selective potent inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity compound 11 (IC50 105 ± 15 nM) is associated 30.7 8.6% proaggregating action on Aβ moderate self-aggregation (34.9 5.4%). Molecular modeling indicates that binding PAS mainly involves (R)-11...
PDE7 inhibitors regulate pro-inflammatory and immune T-cell functions, are a potentially novel class of drugs especially useful in the treatment wide variety inflammatory disorders. Starting from our lead family thioxoquinazolines, we designed, synthesized, characterized series thioxoquinazoline derivatives. Many these compounds showed inhibitory potencies at sub-micromolar levels against catalytic domain PDE7A1 micromolar level PDE4D2. Cell-based studies that not only increased...
New standards for passive immunity in dairy calves from U.S. operations recommend serum IgG concentrations of ≥ 25 g/L at least 40% the calves. To achieve this level maternal colostrum (MC), a single feeding 300 g within 2 h or 400 multiple feedings 24 is recommended. However, similar recommendations do not exist when replacers (CR) need to be used. The objective study was determine if by different replacement protocols resulted excellent transfer (serum > g/L).
The influence of the insertion/addition a benzene ring to natural nucleic acid bases on local aromaticity so-called size-expanded (xN, with N being adenine, guanine, cytosine, and thymine) is examined. To this end, six- five-membered rings in both their benzoderivatives determined using HOMA, NICS, aromatic fluctuation index (FLU), para-delocalization (PDI) descriptors. In general, there good correspondence between different indices, so that moieties more negative NICS values also have...
The tautomeric equilibria of 2-(4'-hydroxyphenylazo)benzoic acid (HABA) and 2-(3',5'-dimethyl-4'-hydroxyphenylazo)benzoic (3',5'-dimethyl-HABA) have been studied by a combination spectroscopic computational methods. For neutral HABA in solvents different polarity (toluene, chloroform, DMSO, DMF, butanol, ethanol) the azo tautomer (AT) is largely predominant. monoanionic HABA, hydrazone (HT) only detected species apolar such as toluene while AT water mixture both tautomers ethanol. Comparison...
Naphtho-homologated DNA bases have been recently used to build a new type of size-expanded known as yyDNA. We theoretical techniques investigate the structure, tautomeric preferences, base-pairing ability, stacking interactions, and HOMO−LUMO gaps naphtho-bases. The structure these is found be similar that benzo-fused predecessors (y-bases) with respect planarity aromatic rings amino groups. Tautomeric studies reveal canonical-like forms naphtho-thymine (yyT) naphtho-adenine (yyA) are most...
The structural, tautomeric, hydrogen-bonding, stacking, and electronic properties of a seleno-derivative thymine (T), denoted here as 4SeT created by replacing O4 in T with Se, are investigated means ab initio computational techniques. structural very similar, the geometrical differences mainly limited to adjacent environment C−Se bond. canonical "keto" form is most stable tautomer, gas phase aqueous solution, for both 4SeT. It argued that competition between two opposite trends, i.e.,...
Among the distinct strategies proposed to expand genetic alphabet, size-expanded nucleobases are promising for development of modified DNA duplexes with improved biotechnological properties. In particular, built up by replacing canonical bases corresponding benzo-fused counterparts could be valuable as molecular nanowires. this context, study reports results classical dynamics simulations carried out examine structural and dynamical features DNAs, including both hybrid containing mixed pairs...
The tautomeric properties of benzoderivatives the canonical nucleic acid bases have been studied by using different computational approaches. Attention has paid to impact benzene group in altering preferences both gas phase and aqueous solution. To this end, relative solvation free energies tautomers determined from Self-Consistent Reaction Field continuum calculations Monte Carlo-Free Energy Perturbation are combined with gas-phase tautomerization quantum mechanical calculations. results...
Abstract Size‐expanded DNA bases are analogues of natural that can be described as a synthesis between benzene and base. have been combined with to form xDNA yDNA, new class synthetic nucleic acids. We interested in yDNA because they might function molecular wires. Recently, we also became intrigued by the possibility altering electronic conductivity means structural changes constituent bases. This appeared after noticed highest occupied orbital–lowest unoccupied orbital (HOMO–LUMO) gap base...
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for have recently become available and started to be administered population in various countries, there is still a strong urgent need treatments cure COVID-19. One safest fastest strategies represented drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from chemical library Phase...
The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1 -adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as repositioned treatment reduce chorea in Huntington's disease (HD).A randomized, placebo-controlled proof-of-concept study was performed 32 HD patients allocated arms 4 sequential 6-week periods each. Patients received placebo at 100 200 mg twice daily crossover design. primary...