Search

The incidence of cancer is rising globally. In this study, the cytotoxic effects of Alcea rosea L., hexane seed (ARHS) extract were examined against liver (HuH-7) and breast (MDA-MB-231) human cancer cell lines, as well as non-cancerous HUVEC cell line. The ARHS extract displayed dose-dependent cytotoxic effects on HuH-7 and MDA-MB-231 cells, with respective IC50 values of 2.39 and 5.67 mg/mL. Additionally, the ARHS extract impeded the migration of HuH-7 cells in a time-dependent fashion. Morphological assessments showed characteristics indicative of apoptosis in the treated cells. ARHS extract induced ROS production in HuH-7 cells. This study revealed that the A. rosea hexane extract effectively inhibited HuH-7 cell growth by inducing apoptosis, as evidenced by the changes in cell and nuclear morphology observed using DAPI and AO/EBr staining. Heptadeca-8,11-dien-1-yl demonstrated the highest docking score, forming three hydrogen bonds with the amino acids ARG-842A, ALA-1050A, and ASP-1052A in the 4ASD receptor. Although it has potential as an anticancer agent, additional research is needed to explore the in vivo anticancer efficacy. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as crizotinib and alectinib, with the KRASwt and KRAS G12C structures. The binding of crizotinib to KRASwt and KRAS G12C, respectively, indicates interaction energy values (42.77 kcal/mol and 46.20 kcal/mol) which are very similar to those obtained between crizotinib and ALK (42.37 kcal/mol). In turn, alectinib bound to the same site as drugs targeting KRAS and KRAS G12C, and showed interaction energy values (51.74 kcal/mol and 54.69 kcal/mol, respectively) higher than those obtained with ALK (44.94 kcal/mol). Finally, a significant decrease in RAS expression within the RAS/MEK pathway was observed in ALK+ and ALK 1196M lung cancer cell lines treated with crizotinib and alectinib. Conclusions: In silico techniques of this study demonstrate the potential binding of ALK inhibitors (crizotinib and alectinib) to the KRAS structure. In addition, this allows suggesting a possible combined therapy between KRAS and ALK inhibitors for cases of coexistence of both mutations that can be assessed in subsequent trials with cell lines. [ABSTRACT FROM AUTHOR]

Copyright of Revista Cientifica de la Facultade de Veterinaria is the property of Universidad del Zulia, Facultad de Ciencias Veterinarias and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

P450 family, especially CYP51 protein, is a common target for the design of antifungal and antiprotozoal drugs. Designing new effective drugs against these pathogens is a necessity and a challenge for the scientific community. To this end, they are evaluated by molecular docking of five schemes of aryl-substituted imidazoles and pseudopeptic imidazoles against CYP51 proteins from different pathogens and against the similar human protein to estimate their selectivity. Once these calculations have been carried out, none of the compounds studied appears to be an effective inhibitor against CYP51- L.infantum. However, for all the remaining proteins lower normalized coupling scores are obtained, fundamentally for schemes 1 and 3. Given the geometry of the proteinlinked complexes formed, schemes 2 and 4 appear to be more selective than schemes 1, 3 and 5. However, the highest estimated selectivity values are obtained for schemes 1 and 3 against CYP51-C.glabrata and for scheme 1 against CYP51-N.fowleri. In general, the direct relationship between the stability of the protein-ligated complex with the direct interaction of the ligand with the Fe2+ cation of the heme group, which provides stability to the union. [ABSTRACT FROM AUTHOR]

Introduction: Computational search of new compounds for future drug therapies against leishmaniasis has focused on trypanothione reductase. This enzyme is essential for the survival of Leishmania infantum, the absence in the host and its high druggability make it a good target for the development of new drugs. The use of plants for phytotherapeutics purpose has been widely investigated due to its important leishmanicidal activities. Aim: The aim of this study was to analyze the interactions of Moringa oleifera compounds to the catalytic and FAD-NADPH binding site of L. infantum trypanothione reductase using molecular docking. Method: Thirty compounds described in M. oleifera species were evaluated and subjected to computational semi-flexible molecular docking assays with the catalytic site and the FAD-NADPH binding domain of the enzyme. Results: The results show that the compounds that demonstrated favorable binding energy values with the catalytic site of the enzyme were apigenin, quercetin, myricetin and isorhamnetin. While the compounds that exhibited favorable binding with the FAD-NADPH domain were rutin and 5,6,7,8-tetrahydrofolic acid. Conclusion: These findings suggest that mentioned M. oleifera compounds present binding affinities for the catalytic site and the FAD-NADPH binding domain of L. infantum trypanothione reductase and could be used for in vitro assays. [ABSTRACT FROM AUTHOR]

A la fecha se han empleado diferentes métodos basados en la estructura para cuantificar las interacciones receptor-ligando, y a partir de estas predecir la energía libre de asociación que proporcionara un estimado de la afinidad de un compuesto por una diana terapéutica. Entre estos métodos está el acoplamiento molecular y las simulaciones de dinámica molecular en conjunto con métodos de cálculo de energía libre de asociación. El acoplamiento molecular, aunque tiene un alto potencial selectivo posee un éxito limitado en la precisión de la estimación de la energía de solvatación y consideración de cambios en la entropía conformacional. Por lo tanto, se ha recurrido a técnicas computacionales más eficientes que predicen la energía libre de unión de una manera más precisa, como lo son los métodos que combinan mecánica molecular con métodos de cálculo de energía. En este contexto, los métodos MMPBSA y MMGBSA permiten predecir la energía libre de unión usando mecánica molecular y modelos continuos de solvatación implícita. Estas técnicas han facilitado la identificación de diferentes compuestos con alta afinidad por una diana farmacológica. En este artículo científico describiremos las bases fundamentales de los métodos MMPBSA y MMGBSA, así como algunos avances relacionados con el empleo de ambos métodos.

Introducción: los cannabinoides son derivados de la planta de cannabis, y han captado la atención por sus efectos terapéuticos demostrados como antiinflamatorios, analgésicos, antieméticos y antitumorales. Su potencial radica en su interacción con los receptores endocannabinoides CB1 y CB2, confirmada por estudios in vitro e in vivo. Por ello, resulta interesante estudiar dicha interacción proteína-ligando mediante técnicas de acoplamiento molecular. Estos permiten describir las zonas de los cannabinoides responsables de su actividad biológica, posibilitando que estos compuestos den respuesta a patologías relacionadas con el sistema inmune. Objetivo: estudiar las interacciones proteína-ligando de 30 cannabinoides análogos del receptor CBN II. Métodos: el grupo de moléculas estudiadas en esta investigación incluyó cannabinoides endógenos, fitocannabinoides y cannabinoides sintéticos, con 30 análogos extraídos de PubChem. Se seleccionó la estructura 3D del receptor CB2 de Protein Data Bank con código 5ZTY. Se optimizó el receptor y ligandos para el acoplamiento molecular, validado con un RMSD de 1.76. Resultados: los ligandos SR141716, AM251 y JZL184 mostraron mejor afinidad por CB2. La fenilalanina fue el aminoácido más presente en la unión, con interacciones alquil y pi-alquil, sugiriendo la importancia de anillos aromáticos. Esto concuerda con otros estudios que indican que los grupos cetona en posición 3 del indol y grupos hidroxilo/metoxilo en posición 6 influyen en la afinidad de unión a CB2 mediante donación de hidrógeno al carbonilo del ligando. Conclusión: los análogos SR141716, AM251 y JZL184, relacionados con el THC y el CBD, se perfilan como moléculas prometedoras para evaluación experimental debido a su alta afinidad por el receptor CB2. Estos compuestos podrían presentar efectos beneficiosos mediados por CB2 en el tratamiento del dolor, inflamación, cáncer y trastornos inmunológicos.

Introducción: las quitinasas son enzimas modificadoras de quitina y se han reportado como alérgenos en plantas y poco en animales, aunque poseen reactividad cruzada debido a su alta conservación. Objetivo: explorar el potencial alergénico y el mimetismo molecular entre quitinasas de fuentes alergénicas comunes mediante bioinformática. Métodos: se utilizaron ElliPro y BepiPred para predecir epítopos de células B y T. Se realizaron estudios filogenéticos, de identidad y de conservación estructural con MEGA 5, PRALINE y Consurf. Se obtuvieron modelos 3D de quitinasas no reportadas en el Protein Data Bank mediante Swiss model. La capacidad de unión de ligandos se exploró con AutoDock Vina, utilizando Bisdionina C, Bisdionina F y Montelukast como ligandos. Resultados: la quitinasa de P. americana (Per a 12) comparte un 44% de identidad con homólogos en P. vannamei, ácaros e insectos, y una identidad moderada con la quitinasa humana. Se reveló una alta homología estructural. Un epítopo lineal entre los residuos 127 y 144 está altamente conservado en todas las quitinasas. Se predijeron tres epítopos de células T conservados. Las simulaciones de acoplamiento molecular revelaron el sitio activo y el potencial de unión de varios ligandos, identificando residuos críticos. Conclusión: proponemos a las quitinasas como un nuevo grupo potencial de panalérgenos, explicando casos de sensibilización a varias fuentes alérgenas. Dado su homología con proteínas humanas, merece una exploración inmunológica para apoyar su implicación en la respuesta autoinmune.

The protease 3CLpro of the SARS-CoV-2 is a crucial enzyme for viral replication, becoming a highly important therapeutic target. Thymol (2-isopropyl-5-methylphenol), a naturally occurring compound found in thyme, exhibits potential antiviral activity against the 3CLpro protease. In this study, using molecular docking with AutoDockTools-1.5.6, the molecular interaction energies between thymol and amino acid residues in the active site of the protein protease 3CLpro were evaluated. Then, with the Atoms in Molecules (QTAIM) and Non-covalent Interactions (NCI) theories, the types of molecular interactions between identifi ed amino acid residues and thymol were analyzed. Quantum calculations were carried out with the Orca-5.0.3 software using the DFT method with the M06-2X functional and the aug-cc-pVDZ basis set in the gas phase. The molecular docking results indicate that thymol is linked to the 3CL protein with an interaction energy equal to -3.784 kcal/mol. QTAIM analysis indicates the presence of critical binding sites between thymol and residues HIS41 and CYS145. In addition, the formation of a hydrogen bond between the OH group of thymol and the CYS145 residue is observed, which is corroborated by the ELF and NCI analyses. Finally, the NCI method confi rms the presence of Van der Waals interactions with the HIS41 residue. The results suggest that the mechanism of inhibition of the activity of the 3CLpro protein is controlled by molecular interactions such as hydrogen bonding and weak interactions. [ABSTRACT FROM AUTHOR]

Background: the significant role of glutamate-cysteine ligase (GCL) towards the synthesis of glutathione for the sequestration of reactive species as a regulatory point is second to none. However, much still need to be known about the enzyme molecular characterization. Thus, the homology modeling of GCL was carried out using different modeling webserver tools. The quality of the predicted crystal structures of human and mouse GCLs with inhibition were further assessed on molecular interaction with naphthalene and its metabolites. Results: the predicted human GCL and mouse GCL model structures have respective 89.8% and 89.6% residues in the most favored region of the Ramachandran plot. However, the molecular docking interaction study with the assessed ligands revealed two different binding pockets with pi-interactions as major non-covalent bond and better binding scores than glutathione. Conclusion: the predicted model could provide better mechanism of GCL catalysis to preserve its essential residues for reasonable GSH synthesis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurological disorder characterized by progressive memory loss due to biochemical processes of multifactorial origin. This leads to the disruption of neuronal synapses and, as a consequence, to dementia. In the present work, structure-activity relationship and molecular docking studies were performed on two series of compounds with activity against two therapeutic targets for AD: aggregation effect and with inhibitory activity of the enzyme acetylcholinesterase. A significant and predictive model of 50 % inhibitory activity dependence (IC50) was obtained for each series. The molecular docking results predicted the form and mode of interaction of the compounds with each of the targets studied. [ABSTRACT FROM AUTHOR]

Copyright of Bistua: Revista de la Facultad de Ciencias Básicas is the property of Facultad de Ciencias Basicas de la Universidad de Pamplona and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

El objetivo del presente trabajo fue realizar un estudio QSAR considerando quinolonas comerciales para el desarrollo de nuevas estructuras químicas con posible acción antibiótica. Además, se complementó con un ensayo de acoplamiento molecular para conocer la interacción molecular entre las moléculas estudiadas y la ADN girasa-topoisomerasa IV (ADNg-TIV) de Staphylococcus aureus (S. aureus). Subsecuentemente, se realizó el acoplamiento molecular in silico de un modelo de TiO2 como vehículo de quinolonas. Todo esto fue desarrollado a partir de la teoría de funcionales de la densidad (DFT, por sus siglas en inglés), con el funcional M06L y un conjunto de base 6-31G(d,p); el docking molecular se realizó considerando la función de scoring MolDock Score. A partir de los resultados obtenidos en el estudio QSAR, se logró diseñar una familia de moléculas con valores de concentración inhibitoria mínima (MIC, por sus siglas en inglés) hasta mil veces menores que los fármacos comerciales; principalmente adicionando sustituyentes azoles e isatinas a los núcleos base. Los acoplamientos moleculares de nuestras moléculas diseñadas imitaron el mecanismo de acoplamiento con el blanco biológico como se ha reportado en la literatura. Estos resultados fueron aún más alentadores, mostrando energías más bajas y estables cuando las quinolonas interactúan con un nanoacarreador de TiO2. Finalmente, podemos concluir que obtuvimos cuatro moléculas con alto potencial debido a su MIC calculado, las cuales potencializan su acoplamiento molecular al utilizar un nanoacarreador de TiO2, siendo una propuesta sólida para futura síntesis y pruebas in vitro.

The subspecies Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei are the causative agents of leishmaniasis, American trypanosomiasis and human African trypanosomiasis respectively. These diseases are not prioritized on the bigger pharmaceutical companies, since they usually affect the poorest countries and the drugs that are available for their treatment are inefficient, old and toxic. In order to find pharmacological alternatives, the following investigation is carried out, which explores in silico study through molecular docking, the difference of using phenyl or furyl groups in positions 4 and 5 of imidazoles as potential antiprotozoa against Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei. It seems to be a general rule that phenyl groups achieve a greater decrease in free binding energy, which indicates a greater affinity for the proteins studied, however there are exceptions due to geometric particularities of the active sites and the structures of the imidazoles. [ABSTRACT FROM AUTHOR]

The study assessed the probable effects of naphthalene exposure through in vivo and in silico approaches. The in vivo assessment was carried on the glutathione (GSH) level in twenty-four Wistar Rats in two main groups based on different exposure times (2 and 4 h). These two groups were sub-grouped into three groups of four rats per group for 14 days. The in silico study was done on naphthalene and its metabolite towards glutamate-cysteine ligase (GCL) (the regulatory enzyme in GSH synthetic pathway) and glutathione reductase (GR). The result revealed that for 2 h of naphthalene exposure, the lower dose (0.75 g/m3) showed the highest reduced GSH level (93.50 ± 4.33 µmol/L) while the higher dose (1.50 g/m3) showed the least reduced GSH level (59.25 ± 7.57 µmol/L). In almost similar pattern, the 4 h exposure of naphthalene at both doses depicted a significant reduction compared to the control. The molecular docking study substantiated with the dynamics study revealed that naphthalene and all its metabolites had better binding score than glutathione (4.63 ± 0.15 kcal/mol) towards GCL with a common interacting residues (Leu-62, Val-63, Arg-64 and Phe-96). However, 4-hydroxychalcone had the best binding score (7.43 ± 0.58 kcal/mol) towards GR compared naphthalene and its metabolites. This study suggested that all naphthalene metabolites could possess more inhibitory potency than naphthalene towards GCL (except naphthalene epoxide) and GR. [ABSTRACT FROM AUTHOR]

There is an important activity of 4-thiazolidinone derivatives on the active site of protein kinases of the parasite Toxoplasma gondii. The calcium-dependent protein kinase CDPK1 is an important object of study, due to its activity in host cell invasion and parasite motility. Twelve structural modifications with alkyl, aromatic and bumpedkinase substitutions at position 3 of the 2-hydrazono-4-thiazolidinone derivative were proposed. A molecular docking and ADME-T properties study was carried out, where derivatives 8A, 2B and 3C presented low binding energy scores (-9.51, -9.19, -10.58) Kcal/mol respectively, a good toxicological profile and no violation of Lipinski's rules being candidates for synthesis for in vivo evaluation. [ABSTRACT FROM AUTHOR]

The influenza A virus is responsible for bird flu; a pathological condition that mainly affects birds, horses, and marine mammals, however, the H5N1 subtype can infect humans quickly; exposing them to a possible pandemic event. Therefore, the objective of this study was to carry out the molecular docking and threedimensional homology modeling of flavonoids derived from amentoflavone with H1N1 and H5N1 neuraminidases of the avian influenza virus. Initially, the 3D structure of H1N1 neuraminidase was obtained by homology. Then, the molecular docking of H1N1 was carried out with six ligands (F36, Ginkgetin, 3S, 3R, 5S, 5R, 6S, and 6R), and subsequently H5N1 and F36, Ginkgetin, 5R, and 6R ligands. Finally, an interaction analysis of the proteinligand complex was performed. The results showed a relationship between the inhibitory activity of ligands and the hydrophobic and hydrogen bridge-type interactions. In addition, an improvement in the inhibitory activity of the ligands for R-type stereochemistry and small bulky substituents was observed. Thus, the experimental evaluation of the 5R and 6R ligands as potential H5N1 inhibitors is proposed. [ABSTRACT FROM AUTHOR]

Introduction: Chagas disease is endemic to the tropical areas of Latin America and has an important prevalence, however, there are few treatments available in the market, so the search for molecules with pharmacological potential that can act in the same way as the disease, it is necessary considering the serious complications. Aim: to evaluate the possible target proteins available in the PDB database, considering the similarity with human proteins as an initial parameter and identify potential inhibitors of the chosen target using molecular docking. Methodology: an evaluation of the parasite proteins was carried out by means of sequence alignment and subsequently a virtual molecular coupling screening was performed with databases and computer resources available at Centro de Cómputo Avanzado de Universidad de Texas (TACC), and the best results were evaluated based on affinity, pharmacokinetics, and toxicity. Results: the molecular target chosen was the dUTPase. After virtual screening, 12 moles showing inhibitory potential were selected of these, 4- {3- [3- (trifluoromethyl) phenyl] isoxazole-5-yl} pyrimidine-2-amine is one of the molecules with the best profile to become a candidate in the treatment of Chagas disease. [ABSTRACT FROM AUTHOR]

El creciente desarrollo de resistencia a antibióticos por parte de mundo microbiano es un problema cada vez mayor y en respuesta nuevas moléculas con potencial antimicrobiano están siendo estudiadas, entre ellas los péptidos antimicrobianos como las Cruzioseptinas. Este trabajo presenta un estudio computacional preliminar de la Cruzioseptina CC-16 extraída del exudado de la piel de la rana Cruziohyla calcarifer. Con base en la secuencia de aminoácidos del péptido se llevaron a cabo diferentes estudios computacionales, entre ellos, la predicción de las propiedades fisicoquímicas y la estructura secundaria. Además de esto se efectuó el acoplamiento molecular de la Cruzioseptina CC-16 con diferentes enzimas de importancia biológica para microrganismos como Escherechia coli, Staphylococcus aureus y Candida albicans, y con moléculas presentes en la membrana celular bacteriana. Los resultados mostraron que la Cruzioseptina CC-16 es un péptido de 23 residuos de largo con una conformación alfa helicoidal predominante, un punto isoeléctrico de 10,73, una carga de +3 de carácter básica y una carga neta a pH 7 de +3,1, además de tener más del 50 % de su estructura conformada por aminoácidos hidrofóbicos, clasificando como un péptido antimicrobiano catiónico. Los estudios preliminares de acoplamiento molecular muestran que un mecanismo de acción basado en inhibición enzimática no es posible, debido principalmente al tamaño del péptido, mientras que un mecanismo con base en un ataque concentrado en la membrana microbiana puede ser viable, debido a las interacciones electrostáticas de la Cruzioseptina CC-16 con diferentes componentes de la membrana.

The computer-aided drug design uses computational chemistry tools to discover, enhance or study drugs related to biologically active molecules. Here, we developed a molecular docking integrated and distributed platform (MODIP) for the virtual screening of bioactives compounds. MODIP is a webserver application, which downloads and prepares the compounds from the PubChem BioAssay database in a suitable format for docking with Autodock vina. The platform is able to screen in parallel chemotherapeutic receptors and its off-targets related proteins. MODIP can be run locally and is adaptable for running others public docking software and chemical databases. [ABSTRACT FROM AUTHOR]

La industria farmacéutica está en constante evolución, siendo el desarrollo y descubrimiento de nuevos fármacos el motor de la misma. Antaño, el diseño de fármacos estaba directamente relacionado a los productos naturales, que posteriormente se modificaban por síntesis. Si bien, la estrategia sigue vigente, el desarrollo de nuevos fármacos implica una inversión considerable de dinero y tiempo. Actualmente, el desarrollo de computadoras más potentes y eficientes ha permitido generar metodologías y simulaciones que han optimizado y en cierto grado modificado el panorama farmacéutico. Aquí se presenta un texto introductorio, a los principales métodos y técnicas computacionales auxiliares en el proceso de diseño y modelado molecular. Se hace especial énfasis en métodos quimioinformáticos, sus conceptos, bases y sus aplicaciones.

Bioactive peptides have been extensively applied for developing health-promoting foods. To improve the value of Laminaria japonica proteins (LJPs), anti-hypertensive peptides were prepared by using controlled enzymatic hydrolysis along with response surface methodology to improve their yields. Eight anti-hypertensive peptides with tyrosine (Tyr) at the C-terminal were determined through an efficient RP-HPLC method and molecular docking was performed to reveal the underlying mechanisms behind their effectiveness of anti-hypertension. According to the results, the strongest activity of hydrolysates was achieved under enzyme ratio (papain: alcalase: trypsin) 1:2:1, pH 8.0, temperature 60°C, substrate concentration 1.7%, enzyme addition 4.4%, and hydrolysis time 5.1 h. Furthermore, molecular docking results displayed that anti-hypertensive peptides could bind with ACE active sites through forming a stable composite structure, thus causing a significant reduction to activities. These results demonstrated the potential applications of LJPs as a source of anti-hypertensive peptides and provided a reference for the industrialized anti-hypertensive productions. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) was declared as pandemic on March 2020 by the World Health Organization. This respiratory disease is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and current efforts are focused in finding pharmaceutical alternatives and vaccines for both, preventing and treating the infected patients around the world. After quarantine and lockdown periods, the treatment of the disease is still limited to symptomatology management and remission to critical care units of the most severe cases. America accumulate the highest number of cases and casualties and the increased pressure over the economy led to the relaxing of mitigation measures. Several clinical trials involving antivirals have been conducted as available alternatives on the short term to face the increasing rate of contagions while experimental vaccines are properly developed and tested. Scientific literature refers a set of FDA approved drugs as repurposed compounds with potential action on the viral mechanism of SARS-CoV-2. In Colombia some of those substances are currently commercialized as antivirals and antiparasitic over-the-counter drugs, while other drugs also in the panorama are unavailable but potentially accessible in the short term for treating the COVID-19 in Colombia, until a massive vaccination campaign can be deployed in the country. [ABSTRACT FROM AUTHOR]

Phthalimide is considered a scaffold for the development of new anticancer agents. In this work, the antiproliferative activity of forty-three phthalimide derivatives was evaluated against cervical (HeLa), liver (HepG2), breast (4T1) cancer cell lines, and a normal cell line of murine fibroblasts (3T3). Finally, a molecular docking analysis of phthalimide derivatives on the active site of the enzymes DNA methyltransferase 1 (DNMT1) and vascular endothelial growth factor receptor 2 (VEGR2) as potential drug targets was performed. The compounds, C16, E11, and E16 showed the best antiproliferative activity against the cell lines HeLa and 4T1. Only, the compound H16 decreased 32% cell proliferation against HepG2 cell line. The compounds H5, H16, E2, E16, and C1 did not affect the proliferation of the 3T3 cell line. The molecular docking analysis showed that phthalimide derivatives have a greater affinity for DNMT1 than S-adenosyl-l-homocysteine, a potent DNMT1 inhibitor. However, molecular docking results do not correlate with their antiproliferative effects, suggesting another potential mechanism of action for the active compounds. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 (Coronavirus 2 of the severe acute respiratory syndrome; previously 2019- nCoV) and SARS-CoV (coronavirus of the severe acute respiratory syndrome) are closely related viruses, which have no treatment so far. Therefore, the search for new molecules is essential. Objectives: the objective of this study is to use in silico approach to propose antiviral compounds potential for SARSCoV- 2 and SARS-CoV and drug-like properties predictions. Materials and methods: Molecular docking were performed using AutoDock Vina with the molecules that had previously demonstrated drug-like properties. Subsequently, amino acids and the type of interaction involved in the protein-ligand complex were identified. Results: It was possible to identify six potential candidates available in the PubChem database capable of interacting with the 6U7 and 2GTB proteases, which bind to the same active site that lopinavir and remdesivir. Conclusion: Small molecules with drug-like properties could be used as antivirals, after experimental evaluations. [ABSTRACT FROM AUTHOR]

This research article proposes a systematic path for the generation of compounds that inhibit the Ebola virus through a molecular docking study. Ebola virus anchoring occurs in the Niemann Pick C1 (NPC1) protein, which is responsible for transporting cholesterol in the endosome/lysosome system. Molecules that have been experimentally reported as possible virus inhibitors were used to assess a possible competitive inhibition in these molecular systems. Several molecules with affinity energies were taken by the active sites, which allowed to identifying the pharmacokinetic potential of these molecules. Adsorption, distribution, metabolism, and excretion of these molecules were also examined. In conclusion, the results obtained show the great inhibitory potential of the A, B, I, J, and K molecules on the anchoring of the Ebola virus glycoprotein with the Niemann Pick C1 protein. [ABSTRACT FROM AUTHOR]

Limited information on sex pheromone recognition by tea moths, Ectropis obliqua Prout (Lepidoptera: Geometridae), exists for this economically important pest of tea (Camellia sinensis L.; Theaceae). Pheromone binding proteins (PBPs), a sub-family of odorant-binding proteins, control transportation of pheromone molecules that may contribute to the discrimination of sex pheromone components. It has been reported previously that EoblPBP1 gene (a pheromone binding protein of E. obliqua) is highly expressed in antennae of the male moth. Based on this information, a reliable model of EoblPBP1 was constructed by homology modeling using the enantiomers of Z3Z9-6,7-epo-18:Hy docked into the hydrophobic cavity of the model. Docking results suggested similar binding affinities of this enantiomer to EoblPBP1. However, electroantennogram and field trapping experiments of E. obliqua males revealed that response to Z3Z9-(6S,7R)-epo-18:Hy was significantly greater than the opposite configuration, and suggested enantiomeric discrimination could occur on sex pheromone receptors of this species of tea moth. [ABSTRACT FROM AUTHOR]

Copyright of Universitas Scientiarum is the property of Pontificia Universidad Javeriana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

En esta investigación se presenta un estudio computacional de la dermaseptina SP2 (DRS-SP2) extraída de exudado de la piel de la rana Agalychnis spurrelli. Ensayos experimentales han permitido extraer, purificar y obtener la secuencia de aminoácidos de este péptido, además de demostrar sus propiedades antimicrobianas contra Escherichia coli, Staphylococcus aureus y Candida albicans. Con la secuencia dilucidada, se realizó un estudio computacional de la estructura obteniéndose sus propiedades físico-químicas, su estructura secundaria y su similitud con otros péptidos conocidos. Además, se realizó el acoplamiento molecular de este péptido con la membrana celular y varias enzimas conocidas para suprimir a estos microorganismos. Los resultados muestran que la DRS-SP2 es un péptido catiónico α-helicoidal con un punto isoeléctrico de 10,68 y carga positiva +3 a pH fisiológico. Se determinó que su estructura es diferente a todas las dermaseptinas que se encuentran en bases de datos llegando a un porcentaje de identidad máximo del 80 %. Estudios de acoplamiento molecular sugieren que el mecanismo de acción de este péptido no se da por la inhibición de vías enzimáticas vitales para el microorganismo, sino por lisis celular.

The Canarypox virus (CNPV) infects captive and wild canaries and cause high mortality and substantial economic losses especially in Middle East countries. Currently, unapproved and illegally imports of embryo propagated, freeze-dried, and live CNPV vaccines are being used by individuals for personal uses in Iran and the region against canarypox disease. The aim of this work was to prepare the stage for the design of a peptide vaccine against canarypox disease. Two immunogenic CNPV proteins were chosen based on homology to antigens from Poxine®, HP1-440 and FP9 strains in fowlpox virus. MHC II specific epitopes of candidate proteins were characterized using various bioinformatics tools. The predicted epitopes were modeled and docked to HLA-DRB1 0101, 0301, 0401, 0405 and 1501 receptors. The stability of docked complexes was evaluated through molecular dynamic simulations. Also, an experimental epitope in vaccinia virus for MHC I receptors was chosen and its canary homolog was docked to two BF receptors in chicken. Due to the critical role of MHC class II in confronting with poxvirus, the IFNAIILWITYAL, LRQLYDVIIPPR, YYNRITSIHM and YRHDDIIAT epitopes were selected among 13 predicted epitopes for MHC class II receptors after docking and MD evaluations. Moreover, due to its long-lasting CD8+ T cell memory responses, the homolog of an experimental epitope from Vaccinia virus (VP35#1) in Canary was evaluated and proposed as potential epitope SLSAYIVSK. These candidate epitopes of high binding affinities may be considered to be included as most effective epitopes for designing epitope-based vaccines against CNPV infection. [ABSTRACT FROM AUTHOR]

Computational tools have been used to propose molecules derived from cephalosporins with potential antibacterial activity, against strains of Escherichia Coli, with higher affinity as inhibitors of penicillin-binding enzymes and which in turn decrease or do not have affinity for extended-spectrum beta-lactamases. 20 molecules were designed based on the molecular structure of the cephalosporin, the structures were optimized using the density functional theory, molecular descriptors of reactivity were calculated, and in parallel form they were subjected to molecular docking with the enzymes mentioned above. The molecules showed negative binding energy values, 12 molecules showed an orientation and favorable interactions in the active site of the penicillin binding enzyme and thirteen molecules had lower affinity than the native ligand (Cefotaxime) for betalactamase. Three molecules can be considered as potential inhibitors of binding enzymes to resistant penicillins and betalactamases. [ABSTRACT FROM AUTHOR]

Objective: The present work aimed at developing novel hybrid molecules for targeting the prostate cancer. It is observed that two human shock proteins Hsp70 and Hsp90 are over-expressed in prostate cancer making them one of the important drug targets. We have designed and developed twelve new hybrid molecules 6a-j for targeting these proteins. Methods: The designed molecules were prepared following a four step reaction protocol and characterized on the basis of proton NMR and Mass spectrometry. These were subjected to in vitro studies by means of Oncotest and CCK-8 assays with two cell lines DU145 and 22Rv1. The selected molecules 6b and 6i were subjected to molecular docking and then for SPR based affinity assay. Results: Compounds 6b and 6i were found to be highly active anticancer compounds comparable to standard drug enzalutamide. They have significant IC50 and high dock score for the Hsp70 and Hsp90. These compounds are selective and have good binding affinity for the Hsp70 due to high Kd. Conclusion: Compound 6b and 6i can serve as lead molecules for the development of antiprostate cancer drugs with Hsp70 as target. [ABSTRACT FROM AUTHOR]

Copyright of TIP Revista Especializada en Ciencias Químico-Biológicas is the property of Universidad Nacional Autonoma de Mexico, Facultad de Estudios Superiores Zaragoza and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)