Publications by authors named "Jose Daniel Figueroa Villar"

We synthesised and screened 18 aromatic derivatives of guanylhydrazones and oximes aromatic for their capacity to bind to dengue virus capsid protein (DENVC). The intended therapeutic target was the hydrophobic cleft of DENVC, which is a region responsible for its anchoring in lipid droplets in the infected cells. The inhibition of this process completely suppresses virus infectivity.

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The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one () and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from H, C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs.

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In this work, the new diaminochromenes: 2,5-dimono-8-methoxychromeno[4,3,2-][1,6]naphthyridine-4-carbonitrile (), 8-ethoxy-2-imino-3,4-dihydro-2-chromene-3-carbonitrile-4-malononitrile (), 2,5-diamino-8-ethoxychromene[4,3,2-][1,6]naphthyridine-4-carbonotrile (), were synthesized and fully characterized through 600 MHz using H, C, APT, gHSQC, gHMBC, ROESY-1D and gated decoupling C. Further docking studies suggested that these compounds are capable of intercalating with the Drew-Dickerson Dodecamer DNA and, therefore, be candidates to work as effective compounds to decrease the cancer radiotherapy.Communicated by Ramaswamy H.

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Background: Neurotoxic chemical warfare agents can be classified as some of the most dangerous chemicals for humanity. The most effective of those agents are the Organophosphates (OPs) capable of restricting the enzyme Acetylcholinesterase (AChE), which in turn, controls the nerve impulse transmission. When AChE is inhibited by OPs, its reactivation can be usually performed through cationic oximes.

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Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer's, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes.

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Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8).

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Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2H)-ylidene)hydrazinecarboxamide (4) were synthesized and evaluated for their anticholinesterase activities. In vitro tests performed by NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE.

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Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman's test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors.

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Neurotoxic organophosphorus compounds (OPs), which are used as pesticides and chemical warfare agents lead to more than 700,000 intoxications worldwide every year. The main target of OPs is the inhibition of acetylcholinesterase (AChE), an enzyme necessary for the control of the neurotransmitter acetylcholine (ACh). The control of ACh function is performed by its hydrolysis with AChE, a process that can be completely interrupted by inhibition of the enzyme by phosphylation with OPs.

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The objective of this study was to present a reliable and practical example of method validation and uncertainty assessment with an analytical method for the determination of polycyclic aromatic hydrocarbons (PAHs) in urban dust. The method was gas chromatography-mass spectrometry in combination with isotope dilution principle to achieve better accuracy for the results. The method performance parameters for five PAHs were determined (phenanthrene, fluoranthene, benzo[a]anthracene, benzo[a]pyrene and benzo[ghi]perylene); this method was used in the key comparison of CCQM-K50b for PAHs in particulate matter.

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In this study the recombinant enzyme nucleoside hydrolase of Leishmania donovani (rLdNH) was expressed in Escherichia coli in connection with maltose binding protein (MBP). The rLdNH-MBP showed efficient a significant in vitro activity with inosine as substrate. From the coupled reaction with xanthine oxidase (XO) it was possible to determine the kinetic constants of rLdNH-MBP as K(M) (434 ± 109 μM) and V(max) (0.

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Penicillium corylophilum isolated from mosquitoes was cultivated in liquid media leading to the first reported identification of citrinin (1a) as one metabolic component of this fungus. The produced amount of 1a indicated this compound as the most abundant secondary metabolite of this fungus. Stressing the culture of P.

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NMR is one of the most powerful techniques for ligand-biomolecule interaction studies and drug screening and design. There are several methods that are strongly used, including chemical shift perturbation (CSP), saturation transfer difference (STD) and diffusion coefficients. However, one of the most useful and easy to apply NMR parameters in medicinal chemistry studies is the spin-lattice relaxation data, which can be employed to investigate the strength and topology of intermolecular interactions, such as drug-drug, drug-protein, drug-DNA, drug-micelle (or vesicle) and biomolecule-biomolecule interactions.

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In this paper we carried out a comparison between all the possible selective versions of the basic heteronuclear correlation experiment, the FUCOUP sequence. We concluded that the best experiment is that one in which the selective pulse is given in the carbon dimension, which we called SHESSLOC (Selective HEteronuclear Simultaneous Short and LOng-range Correlations). The sensitivity of the sequence was improved with the introduction of pulsed field gradients.

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Three new bisguanylhydrazones analogous to pentamidine were synthesized, fully characterized and tested as anti-Trypanosoma cruzi candidates. Contrary to literature reports, that bicationic compounds are more active than monocationic compounds against Trypanosoma brucei, it was found that these bisguanylhydrazones are much less effective against T. cruzi than simple aromatic monoguanylhydrazones, thus suggesting different mechanism of action for both parasites.

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The biological activity of radiosensitizers is associated to their electron affinity (EA), which can be divided in two main processes: vertical and adiabatic. In this work, we calculated the EAs of nitrofurans and nitroimidazoles (Fig. 2) using Hartree-Fock (HF) and density functional theory (DFT) methods and evaluated solvent effects (water and carbon tetrachloride) on EAs.

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A study of the nature of the anthelmintic p-cresol:piperazine complex in chloroform solution has been conducted using different NMR techniques: self-diffusion coefficients using DOSY; NOE, NULL, and double-selective T1 measurements to determine inter-molecular distances; and selective and non-selective T1 measurements to determine correlation times. The experimental results in solution and CP-MAS were compared to literature X-ray diffraction data using molecular modeling. It was shown that the p-cresol:piperazine complex exists in solution in a very similar manner as it does in the solid state, with one p-cresol molecule hydrogen bonded through the hydroxyl hydrogen to each nitrogen atom of piperazine.

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The development of drug resistance is reducing the efficiency of antifolates as antimalarials. This phenomenon has been linked to the occurrence of mutations in the parasite's dihydrofolate reductase (DHFR). In this way, the resistance to pyrimethamine and cycloguanil, two potent inhibitors of P.

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