RESUMEN

A porphyrin-BODIPY dyad (P-BDP) was obtained through covalent bonding, featuring a two-segment design comprising a light-harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P-BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96 %) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P-BDP effectively induced the photooxidation of L-tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99 %) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P-BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P-BDP presents an interesting photosensitizing structure that takes advantage of the light-harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

Asunto(s)

Compuestos de Boro , Fármacos Fotosensibilizantes , Porfirinas , Staphylococcus aureus , Compuestos de Boro/química , Compuestos de Boro/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Staphylococcus aureus/efectos de los fármacos , Porfirinas/química , Porfirinas/farmacología , Oxígeno Singlete/metabolismo , Oxígeno Singlete/química , Luz , Estructura Molecular

RESUMEN

Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 1, derived from the BPT-containing ligand H3L1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed. Additionally, the stability of the ligands and complexes was monitored by UV-vis spectroscopy in DMSO and biologically relevant media. All the compounds showed moderate to high cytotoxicity towards the triple negative human breast cancer cell line MDA-MB-231. BPT derivatives were the most cytotoxic, specially H3L1, reaching an IC50 value up to the nanomolar range. Finally, fluorescence microscopy imaging studies employing mitochondria- and nucleus-staining dyes showed that the BODIPY-carrying ligand H3L2 was highly cell permeant and suggested that the compound preferentially accumulates in the mitochondria.

Asunto(s)

Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Compuestos de Boro/química , Cobre/química , Tiofenos/farmacología , Antineoplásicos/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Microscopía Fluorescente , Estructura Molecular , Tiofenos/química , Neoplasias de la Mama Triple Negativas

RESUMEN

Organoboron compounds have been playing an increasingly important role in analytical chemistry, material science, health applications, and particularly as functional polymers like boron carriers for cancer therapy. There are two main applications of boron isotopes in radiation cancer therapy, Boron Neutron Capture Therapy and Proton Boron Fusion Therapy. In this study, a novel and original material consisting of a three-dimensional polymer network crosslinked with [Formula: see text]B enriched boric acid molecules is proposed and synthesized. The effects of the exposition to thermal neutrons were studied analyzing changes in the mechanical properties of the proposed material. Dedicated Monte Carlo simulations, based on MCNP and FLUKA main codes, were performed to characterize interactions of the proposed material with neutrons, photons, and charged particles typically present in mixed fields in nuclear reactor irradiations. Experimental results and Monte Carlo simulations were in agreement, thus justifying further studies of this promising material.

Asunto(s)

Compuestos de Boro/química , Boro/química , Polímeros/química , Compuestos de Boro/síntesis química , Fenómenos Químicos , Reactivos de Enlaces Cruzados , Portadores de Fármacos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Poliaminas/química , Polihidroxietil Metacrilato/análogos & derivados , Polihidroxietil Metacrilato/química , Radiación Ionizante

RESUMEN

Herein, we report the use of polylactic acid coated with a halogenated BODIPY photosensitizer (PS) as a novel self-sterilizing, low-cost, and eco-friendly material activated with visible light. In this article, polymeric surfaces were 3D-printed and treated with the PS using three simple methodologies: spin coating, aerosolization, and brush dispersion. Our studies showed that the polymeric matrix remains unaffected upon addition of the PS, as observed by dynamic mechanical analysis, Fourier transform infrared, scanning electron microscopy (SEM), and fluorescence microscopy. Furthermore, the photophysical and photodynamic properties of the dye remained intact after being adsorbed on the polymer. This photoactive material can be reused and was successfully inactivating methicillin-resistant Staphylococcus aureus and Escherichia coli in planktonic media for at least three inactivation cycles after short-time light exposure. A real-time experiment using a fluorescence microscope showed how bacteria anchored to the antimicrobial surface were inactivated within 30 min using visible light and low energy. Moreover, the material effectively eradicated these two bacterial strains on the first stage of biofilm formation, as elucidated by SEM. Unlike other antimicrobial approaches that implement a dissolved PS or non-sustainable materials, we offer an accessible green and economic alternative to acquire self-sterilizing surfaces with any desired shape.

Asunto(s)

Antibacterianos/química , Compuestos de Boro/química , Fármacos Fotosensibilizantes/química , Poliésteres/química , Esterilización , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Compuestos de Boro/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/fisiología , Infecciones por Escherichia coli/prevención & control , Humanos , Fármacos Fotosensibilizantes/farmacología , Poliésteres/farmacología , Impresión Tridimensional , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Esterilización/métodos , Propiedades de Superficie

RESUMEN

BACKGROUND: The number of known boron-containing compounds (BCCs) is increasing due to their identification in nature and innovative synthesis procedures. Their effects on the fungal kingdom are interesting, and some of their mechanisms of action have recently been elucidated. METHODS: In this review, scientific reports from relevant chemistry and biomedical databases were collected and analyzed. RESULTS: It is notable that several BCC actions in fungi induce social and economic benefits for humans. In fact, boric acid was traditionally used for multiple purposes, but some novel synthetic BCCs are effective antifungal agents, particularly in their action against pathogen species, and some were recently approved for use in humans. Moreover, most reports testing BCCs in fungal species suggest a limiting effect of these compounds on some vital reactions. CONCLUSIONS: New BCCs have been synthesized and tested for innovative technological and biomedical emerging applications, and new interest is developing for discovering new strategic compounds that can act as environmental or wood protectors, as well as antimycotic agents that let us improve food acquisition and control some human infections.

Asunto(s)

Antifúngicos/farmacología , Compuestos de Boro/farmacología , Hongos/efectos de los fármacos , Antifúngicos/síntesis química , Antifúngicos/química , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Humanos , Pruebas de Sensibilidad Microbiana

RESUMEN

A new BODIPY (BDP 1) bearing a dimethylaminopropoxy group attached to a phenylene unit was synthesized. This compound was brominated to obtain the halogenated analog BDP 2, which was designed to enhance the photodynamic effect of BODIPY to kill bacteria without an intrinsic cationic charge. The basic amino group located at the end of the propoxy bridge can acquire a positive charge by protonation in an aqueous medium, increasing the binding to bacterial cells. Interaction and photokilling activity mediated by these compounds was evaluated in Staphylococcus aureus and Escherichia coli. BDP 1 and BDP 2 were rapidly bound to bacterial cells, showing bioimages with green emission. Complete elimination of S. aureus was detected when cells were incubated with 1 µM BDP 2 and irradiated for 5 min. Comparable photoinactivation was obtained with E. coli, after an irradiation of 30 min. Furthermore, BDP 2 was effective to kill bacteria at very low concentration (0.5 µM). Thus, BDP 1 showed mainly interesting properties as a fluorophore, whereas BDP 2 was highly effective photosensitizer as a broad-spectrum antibacterial agent.

Asunto(s)

Compuestos de Boro/química , Compuestos de Boro/farmacología , Escherichia coli/fisiología , Viabilidad Microbiana/efectos de los fármacos , Viabilidad Microbiana/efectos de la radiación , Fotoquimioterapia , Staphylococcus aureus/fisiología , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Escherichia coli/efectos de la radiación , Imagen Molecular , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/efectos de la radiación , Factores de Tiempo

RESUMEN

One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy.

Asunto(s)

Terapia por Captura de Neutrón de Boro , Lapatinib/uso terapéutico , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Animales Recién Nacidos , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Humanos , Concentración 50 Inhibidora , Lapatinib/química , Lapatinib/farmacología , Ratones , Inhibidores de Proteínas Quinasas/farmacología , Triazinas/síntesis química , Triazinas/química

RESUMEN

Boron nitride nanotubes (BNNTs) have been growing in notoriety in the development of systems aiming bioapplications. In this work we conducted an investigation about the mechanisms involved in the incorporation of samarium and gadolinium in BNNTs. The process was performed by the reduction of samarium and gadolinium oxides (Sm2O3 and Gd2O3, respectively) in the presence of NH3 gas (witch decomposes into N2 and H2) at high temperatures. Various characterization techniques were conducted to elucidate how Sm and Gd are introduced into the BNNT structure. Biological in vitro assays were performed with human fibroblasts and a human osteosarcoma cell line (SAOS-2). Our results show that the studied systems have high potential for biomedical application and can be used as non-invasive imaging agents, such as scintigraphy radiotracers or as magnetic resonance imaging (MRI) contrast medium, being able to promote the treatment of many types of tumors simultaneously to their diagnosis.

Asunto(s)

Compuestos de Boro/química , Gadolinio/química , Nanomedicina , Nanotubos/química , Óxidos/química , Samario/química , Línea Celular , Humanos

RESUMEN

BACKGROUND: Boron is considered a trace element that induces various effects in systems of the human body. However, each boron-containing compound exerts different effects. OBJECTIVE: To review the effects of 2-Aminoethyldiphenyl borinate (2-APB), an organoboron compound, on the human body, but also, its effects in animal models of human disease. METHODS: In this review, the information to showcase the expansion of these reported effects through interactions with several ion channels and other receptors has been reported. These effects are relevant in the biomedical and chemical fields due to the application of the reported data in developing therapeutic tools to modulate the functions of the immune, cardiovascular, gastrointestinal and nervous systems. RESULTS: Accordingly, 2-APB acts as a modulator of adaptive and innate immunity, including the production of cytokines and the migration of leukocytes. Additionally, reports show that 2-APB exerts effects on neurons, smooth muscle cells and cardiomyocytes, and it provides a cytoprotective effect by the modulation and attenuation of reactive oxygen species. CONCLUSION: The molecular pharmacology of 2-APB supports both its potential to act as a drug and the desirable inclusion of its moieties in new drug development. Research evaluating its efficacy in treating pain and specific maladies, such as immune, cardiovascular, gastrointestinal and neurodegenerative disorders, is scarce but interesting.

Asunto(s)

Compuestos de Boro/uso terapéutico , Profármacos/uso terapéutico , Activación Metabólica , Inmunidad Adaptativa/efectos de los fármacos , Compuestos de Boro/química , Compuestos de Boro/farmacología , Calcio/metabolismo , Sistema Cardiovascular/efectos de los fármacos , Sistema Digestivo/efectos de los fármacos , Humanos , Inmunidad Innata/efectos de los fármacos , Modelos Moleculares , Estructura Molecular , Miocitos Cardíacos/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Sistema Nervioso/efectos de los fármacos , Neuronas/efectos de los fármacos , Profármacos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Canales Catiónicos TRPV/química , Canales Catiónicos TRPV/metabolismo

RESUMEN

Aim: The field of nanotechnology promotes the development of innovative and more effective cancer therapies. This work is aimed to develop a hybrid system that combines the capacity of boron nitride nanotubes (BNNTs) to be internalized by tumor cells and the ability of nickel ferrite nanoparticles to efficiently release heat by induced AC magnetic heating. Materials & methods: The systems studied were characterized by using x-ray diffractometry, transmission electron microscopy, vibrating sample magnetometry and Mössbauer spectroscopy. Results: The ferrite nanoparticles attached to BNNT were able to achieve the required temperatures for magnetohyperthermia therapies. After cellular internalization, AC induced magnetic heating of BNNT@NiFe2O4 can kill almost 80% of Hela cells lineage in a single cycle. Conclusion: This system can be a highly efficient magnetohyperthermia agent in cancer therapy.

Asunto(s)

Compuestos de Boro/química , Nanopartículas/química , Nanotecnología/métodos , Nanotubos/química , Compuestos Férricos/química , Células HeLa , Humanos , Níquel/química

RESUMEN

The controlled synthesis of hybrid two-dimensional (2D) materials and the development of atomically precise nanopore fabrication techniques have opened up entirely new possibilities for sensing applications via nanoelectronics. Here, we investigate the electronic transport properties of an in-plane hybrid graphene/h-BN device, containing a graphene nanopore, to assess its feasibility to act as a molecular sensor. The results from our calculations based on density functional theory and the non-equilibrium Green's function formalism reveal the capability to confine the electric current pathways to the two carbon wires lining either edge of the nanopore, thereby creating conditions in which the conductance is highly sensitive to any changes in the electrical potential inside the nanopore. We apply this setup to assess whether it is possible to electrically determine the base sequence in a DNA molecule. Indeed, the modulation of the device conductance reveals a characteristic fingerprint of each nucleotide, which manifests itself in a pronounced difference in the sensitivity of the four different nucleotides, thereby allowing electrical discrimination. These findings lead us to propose this device architecture as a promising nanobiosensor. While fabrication in the lab may represent a profound experimental challenge, it should nevertheless in principle be feasible with existing contemporary techniques of hybrid 2D material synthesis, in conjunction with approaches for highly controlled nanopore creation.

Asunto(s)

ADN/análisis , Nanoporos , Nanotecnología , Compuestos de Boro/química , Teoría Funcional de la Densidad , Electricidad , Transporte de Electrón , Grafito/química

RESUMEN

Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.

Asunto(s)

Ácido Fólico/química , Nanopartículas/química , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Rastreo Diferencial de Calorimetría , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Endocitosis/efectos de los fármacos , Femenino , Humanos , Neoplasias Ováricas/patología , Paclitaxel/farmacología , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/síntesis química , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

In this work we describe not previously explored binding studies on the reversible interaction of benzoxaborole with ligands of medical and pharmaceutical interest such as nucleosidic drugs gemcitabine and capecitabine, as well as the hydrophobic chemotherapeutic doxorubicin. We include functional derivatives of benzoxaborole such as a near infrared fluorescent boronolectine, Cy-Bx, The dynamic covalent interaction in physiological conditions was assessed by spectroscopic techniques yielding moderate to high binding affinities. The cytotoxic activity of the drugs upon conjugation to the boronolectins was evaluated revealing significant influence of the bioconjugation status on the cellular viability. The availability of the conjugate for cellular uptake and localization in the model cancer cell line HeLa was assessed by fluorescence imaging. Benzoxaborole and the fluorescent boronolectin Cy-Bx, proved to be versatile conjugation tools for 1,2 and 1,3-diol containing pharmacophores as well as bioisosteric forms such as 1,2-hydroxyamino, envisioning these small boronolectins as components in systems for drug release with tracking capability.

Asunto(s)

Antineoplásicos/farmacología , Benzamidas/química , Compuestos de Boro/farmacología , Doxorrubicina/farmacología , Nucleósidos/química , Nucleósidos/metabolismo , Antibióticos Antineoplásicos/farmacología , Antineoplásicos/química , Compuestos de Boro/química , Proliferación Celular , Doxorrubicina/química , Liberación de Fármacos , Colorantes Fluorescentes/química , Células HeLa , Humanos , Monosacáridos/química

RESUMEN

A covalently linked BODIPY-fullerene C60 dyad (BDP-C60 ) was synthesized as a two-segment structure, which consists of a visible light-harvesting antenna attached to an energy or electron acceptor moiety. This structure was designed to improve the photodynamic action of fullerene C60 to inactivate bacteria. The absorption spectrum of BDP-C60 was found to be a superposition of the spectra of its constitutional moieties, whereas the fluorescence emission of the BODIPY unit was strongly quenched by the fullerene C60 . Spectroscopic, calculations, and redox studies indicate a competence between photoinduced energy and electron transfer. Protonating the dimethylaminophenyl substituent through addition of an acidic medium led to a substantial increase in the fluorescence emission, triplet excited state formation, and singlet molecular oxygen production. At physiological pH, photosensitized inactivation of Staphylococcus aureus mediated by 1 µM BDP-C60 exhibited a 4.5 log decrease of cell survival (>99.997 %) after 15 min irradiation. A similar result was obtained with Escherichia coli using 30 min irradiation. Moreover, proton-activated photodynamic action of BDP-C60 turned this dyad into a highly effective photosensitizer to eradicate E. coli. Therefore, BDP-C60 is an interesting photosensitizing structure in which the light-harvesting antenna effect of the BODIPY unit combined with the protonation of dimethylaminophenyl group can be used to improve the photoinactivation of bacteria.

Asunto(s)

Antiinfecciosos/química , Compuestos de Boro/química , Compuestos de Boro/farmacología , Fulerenos/química , Fulerenos/farmacología , Complejos de Proteína Captadores de Luz/química , Electroquímica , Escherichia coli/efectos de los fármacos , Estructura Molecular , Fotoquimioterapia , Staphylococcus aureus/efectos de los fármacos

RESUMEN

In the search of nanomaterials to be used in drug delivery applications, Density Functional Theory calculations were implemented to study the interaction between graphene (G) and hexagonal boron nitride nanosheet (hBNN) with octahedral B12N12 fullerenes. These B12N12 fullerenes were considered in two cases: pristine and the modified one with boron-boron, nitrogen-nitrogen (tetragon) and boron-boron-boron (hexagon) homo-nuclear bonds. The whole systems were analyzed in the gas and aqueous phases. The results reveal for all these systems that the interaction is in the range of physisorption (Eads = from -0.03 to -0.37 eV) for both phases, limiting its functions as a vehicle. However, for the nano-composite: B12N12 fullerene modified and hBNNs, the values of average chemical reactivity and HOMO-LUMO gap decreased whereas the polarity was improved, thereby this combination of quantum descriptors lead them to be considered as potential vehicle for drug delivery.

Asunto(s)

Compuestos de Boro/química , Fulerenos/química , Grafito/química , Nanoestructuras/química , Teoría Funcional de la Densidad , Modelos Moleculares , Conformación Molecular , Análisis Espectral

RESUMEN

BACKGROUND: Single Boron Atom Compounds (SBACs) have been used for drug discovery in diseaseassociated proteins due to the empty p-orbital in the atomic structure of boron, which allows it to experience diverse binding modes during molecular recognition with a range of proteins. OBJECTIVE: During the molecular recognition process with a protein target, SBACs can assume an anionic tetragonal arrangement or a neutral trigonal planar structure to produce four possible reversible covalent or non-covalent binding modes with a protein. However, the development of new SBACs has been hampered by the fact that most of the force fields present in many of the software packages used in drug design lack the various types of boron atom parameters. METHODS: We review in silico studies in which a series of theory-based computational strategies have been used to overcome the lack of boron parameters in most of the force fields used in drug design. RESULTS: The modeling studies discussed in this review have provided substantial insight into the molecular recognition of SBACs targeting different receptors, including the elucidation of some of the key interactions, which serve as a guide for the development of selective SBACs. CONCLUSION: Although the strategies employed in many of the studies presented here should serve in the development of selective SBACs, it is clear that the development of the precise force field parameters, which include not only the individual atom types but also the entire molecule, is still lacking, yet it is a necessary requirement for the design of new SBACS as well as for gaining insight into their molecular recognition.

Asunto(s)

Compuestos de Boro/química , Descubrimiento de Drogas , Simulación de Dinámica Molecular , Compuestos de Boro/síntesis química , Programas Informáticos

RESUMEN

Human arginase I (hARGI) is an important enzyme involved in the urea cycle; its overexpression has been associated to cardiovascular and cerebrovascular diseases. In the last years, several congeneric sets of hARGI inhibitors have been reported with possible beneficial roles for the cardiovascular system. At the same time, crystallographic data have been reported including hARGI⁻inhibitor complexes, which can be considered for the design of novel inhibitors. In this work, the structure⁻activity relationship (SAR) of Cα substituted 2(S)-amino-6-boronohexanoic acid (ABH) derivatives as hARGI inhibitors was studied by using a three-dimensional quantitative structure⁻activity relationships (3D-QSAR) method. The predictivity of the obtained 3D-QSAR model was demonstrated by using internal and external validation experiments. The best model revealed that the differential hARGI inhibitory activities of the ABH derivatives can be described by using steric and electrostatic fields; the local effects of these fields in the activity are presented. In addition, binding modes of the above-mentioned compounds inside the hARGI binding site were obtained by using molecular docking. It was found that ABH derivatives adopted the same orientation reported for ABH within the hARGI active site, with the substituents at Cα exposed to the solvent with interactions with residues at the entrance of the binding site. The hARGI residues involved in chemical interactions with inhibitors were identified by using an interaction fingerprints (IFPs) analysis.

Asunto(s)

Aminocaproatos/química , Aminocaproatos/farmacología , Arginasa/antagonistas & inhibidores , Compuestos de Boro/química , Compuestos de Boro/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad Cuantitativa , Arginasa/química , Humanos , Concentración 50 Inhibidora , Ligandos

RESUMEN

A new series of dendronized bodipys containing pyrene units was synthesized and characterized. Their optical and photophysical properties were determined by absorption and fluorescence spectroscopy. This series includes three different compounds. The first one has an anisole group linked to the bodipy unit, which was used as the reference compound. In the second, the bodipy core is linked to a zero generation dendron with one pyrene unit. The third compound contains a first generation Fréchet-type dendron bearing two pyrene units. In this work, the combination pyrene-bodipy was selected as the donor-acceptor pair for this fluorescence resonance energy transfer (FRET) study. Doubtless, these two chromophores exhibit high quantum yields, high extinction coefficients, and both their excitation and emission wavelengths are located in the visible region. This report presents a FRET study of a novel series of pyrene-bodipy dendritic molecules bearing flexible spacers. We demonstrated via spectroscopic studies that FRET phenomena occur in these dyads.

Asunto(s)

Compuestos de Boro/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Pirenos/química , Antracenos/química , Compuestos de Boro/síntesis química , Análisis Espectral/métodos

RESUMEN

Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)-(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine-phosphorylation-regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds.

Asunto(s)

Antineoplásicos/química , Antineoplásicos/farmacología , Compuestos de Boro/química , Compuestos de Boro/farmacología , Tripanocidas/química , Tripanocidas/farmacología , Tirfostinos/química , Tirfostinos/farmacología , Animales , Antineoplásicos/síntesis química , Compuestos de Boro/síntesis química , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Enfermedad de Chagas/tratamiento farmacológico , Diseño de Fármacos , Humanos , Ratones , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Tripanocidas/síntesis química , Trypanosoma cruzi/efectos de los fármacos , Tirfostinos/síntesis química

RESUMEN

Classical molecular dynamics (MD) and density functional theory (DFT) calculations are developed to investigate the dopamine and caffeine encapsulation within boron nitride (BN) nanotubes (NT) with (14,0) chirality. Classical MD studies are done at canonical and isobaric-isothermal conditions at 298 K and 1 bar in explicit water. Results reveal that both molecules are attracted by the nanotube; however, only dopamine is able to enter the nanotube, whereas caffeine moves in its vicinity, suggesting that both species can be transported: the first by encapsulation and the second by drag. Findings are analyzed using the dielectric behavior, pair correlation functions, diffusion of the species, and energy contributions. The DFT calculations are performed according to the BLYP approach and applying the atomic base of the divided valence 6-31g(d) orbitals. The geometry optimization uses the minimum-energy criterion, accounting for the total charge neutrality and multiplicity of 1. Adsorption energies in the dopamine encapsulation indicate physisorption, which induces the highly occupied molecular orbital-lower unoccupied molecular orbital gap reduction yielding a semiconductor behavior. The charge redistribution polarizes the BNNT/dopamine and BNNT/caffeine structures. The work function decrease and the chemical potential values suggest the proper transport properties in these systems, which may allow their use in nanobiomedicine.

Asunto(s)

Compuestos de Boro/química , Cafeína/química , Dopamina/química , Simulación de Dinámica Molecular , Nanotubos/química , Teoría Funcional de la Densidad , Difusión , Composición de Medicamentos , Termodinámica