Michael González Durruthy

University of Porto | UP · Department of Chemistry

Background The widespread use of new engineered nanomaterials (ENMs) in industries such as cosmetics, electronics, and diagnostic nanodevices, has been revolutionizing our society. However, emerging studies suggest that ENMs present potentially toxic effects on the human lung. In this regard, we developed a machine learning (ML) nano-quantitative-...

Effective and reliable prediction of allosteric molecular interactions involved in protein-ligand systems are essential to understand pharmacological modulation and toxicology processes that are driven by multiple factors covering from the atomistic to cellular level. Even though the interactions taking place within a defined biophysical environmen...

In this study we present an in-depth and detailed analysis of the binding process between two antibiotics (cloxacillin and dicloxacillin) and a blood serum protein (lysozyme). Our objectives have been several: to determine, at the atomic level, the structural and conformational changes that take place in both molecular structures once the complex i...

Aims Herein, molecular docking approaches and DFT ab initio simulations were combined for the first time, to study the key interactions of cyclodextrins (CDs: α-CD, β-CD, and γ-CD) family with potential pharmacological relevance and the multidrug resistance P-gp protein toward efficient drug-delivery applications Background The treatment of neurol...

In this work we present a computational analysis together with experimental studies, focusing on the interaction between a benzothiazole (BTS) and lysozyme. Results obtained from isothermal titration calorimetry, UV-vis, and fluorescence were contrasted and complemented with molecular docking and machine learning techniques. The free energy values...

The development of new materials based on hydroxyapatite has undergone a great evolution in recent decades due to technological advances and development of computational techniques. The focus of this review is the various attempts to improve new hydroxyapatite-based materials. First, we comment on the most used processing routes, highlighting their...

Due to an oversight of the publisher, Page no 2310 was missing in the published paper and page no 2311 repeated twice in the article entitled “Computational Modeling of Environmental Co-exposure on Oil-Derived Hydrocarbon Overload by Using Substrate-Specific Transport Protein (TodX) with Graphene Nanostructures, 2020, 20(25), 2308-2325 [1]. The pag...

The tau protein is considered an important qualitative and quantitative biomarker for Alzheimer’s disease in its asymptomatic phase. In 2011, biomarkers were suggested by the National Institute on Aging-Azheimer’s Association as a new criterion for the early diagnosis of Alzheimer’s disease. Thus, highlighting the non-existence of theoretical resea...

Our novel strategy for the rational design of immobilized derivatives (RDID) is directed to predict the behavior of the protein immobilized derivative before its synthesis, by the usage of mathematic algorithms and bioinformatics tools. However, this approach needs to be validated for each target enzyme. The objective of this work was to validate t...

In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and propranolol-with the most abundant blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as compleme...

Herein, we present an integrated computational and experimental study to tackle the interactions between recognized β-lactam antibiotics (cloxacillin and dicloxacillin) with the fibrinogen blood plasma protein. For this purpose, molecular docking simulation with elastic network based on collective low-frequency normal modes and perturbation respons...

Background Bioremediation is a biotechnology field that uses living organisms to remove contaminants from soil and water; therefore, they could be used to treat oil spill from the environment. Methods Herein, we present a new mechanistic approaches combining Molecular Docking Simulation and Density Functional Theory to modeling the bioremediation-...

Three-dimensional conformational crystallographic binding-modes are of paramount importance to understand the docking mechanism of protein-ligand interactions and to identify potential “leading drugs” conformers towards rational drugs-design. Herein, we present an integrated computational-experimental study tackling the problem of multiple binding...

Introduction Monoamine oxidase inhibitors (MAOIs) are compounds largely used in the treatment of the Parkinson’s disease (PD), Alzheimer’s disease and other neuropsychiatric disorders since are closely related to the MAO enzymes activity. The two isoforms of the MAO enzymes, MAO-A and MAO-B are responsible of the degradation of monoamine neurotrans...

Graphical Abstract Abstract. Currently, antioxidant compounds, such as vitamins C and E, are widely used to deactivate free oxygen radical species (ROS), playing an essential role in preventing chronic neurodegenerative diseases where ROS levels are significantly increased 1,2. Herein, single-walled carbon nanocones (SWCNC), a nanocarbon allotrope...

Laccase catalyzes oxidation of lignin and aromatic compound with similar structure to this one. Their low substrate specifi city results on degradation of similar phenolic compounds. In this context, Molecular Docking was performed with different ligands suggesting potential biodegradation. Binding active-sites prediction of fungal laccase (access...

The control of Mg2+ incorporation into HA nanorods gave rise to a tailored crystallinity degree, cell parameters, morphology, surface hydration and solubility2 . Herein, we have developed mechanically robust scaffolds, exhibiting a highly interconnected fiber mesh structure, by optimizing the distribution of HA nano-rods within hydrogels composed b...

Nanotechnology has been an important tool for the production of nanoparticles with controlled release of drugs for therapeutic applications. Here, we produced solid lipid nanoparticles (SLN) loaded with curcumin and capsaicin (NCC) following the overarching goals of green chemistry. Currently, besides evaluating the composition, and size of these,...

We present a computational analysis coupled with experimental studies, focusing on the binding-interaction between beta-adrenoreceptor blocking agents (acebutolol and propranolol) with fibrinogen protein (E-region). Herein, computational modeling on structural validation and flexibility properties of fibrinogen E-region showed that the E-region int...

Background: PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype. Objective: In the present work, we tested a new mechanistic insight on the AZD1208 (...

We present an in-silico approach for modeling the non-covalent interactions between human mitochondrial voltage-dependent anion channel (hVDAC1) with a family of single walled carbon nanotubes (SWCNT) with a defined pattern of topological vacancies (from v = 1 to 16), obtained by removing atoms from the SWCNT surface. The general results showed mor...

Recently, it has been suggested that the mitochondrial oligomycin A-sensitive F0-ATPase subunit is an uncoupling channel linked to apoptotic cell death and as such, the toxicological inhibition of mitochondrial F0-ATP hydrolase can be an interesting mitotoxicity-based therapy under pathological conditions. In addition, carbon nanotubes (CNTs) have...

In the present study, the molecular docking mechanism based on pharmacodynamic interactions between the ligands AZD1208 and recognized chemotherapy agents (Vincristine and Daunorubicin) with human ATP-binding cassette (ABC) transporters (ABCB1) was investigated. For the first time, were combined an in silico approaches like molecular docking and ab...

Although some studies have showed the effects of different crystalline structures of nTiO2 (anatase and rutile) and their applicability in several fields, few studies has analyzed the effect of coexposure with other environmental contaminants such as copper. Thus, the objective of this study was to evaluate if the coexposure to nTiO2 (nominal conce...

La búsqueda de nuevas enzimas de origen marino presenta amplias perspectivas debido a que el mar y los organismos que lo habitan están menos explorados que los organismos terrestres. Esto posibilita encontrar, con altas probabilidades, enzimas con diferentes especificidades hacia sustratos no naturales si las comparamos con las especificidades info...

Experimental studies have shown that hydrophobic nanoparticles like carbon nanotubes (CNT) could be potentially used for the treatment of several neurological disorders like Alzheimer's disease, brain ischemia, and Parkinson. In this regards, it is of fundamental importance to understand the mitochondrial mechanisms involved in these diseases in or...

Several 1,4-dihydropyridine derivatives overcome the multidrug resistance in tumors, but their intrinsic cytotoxic mechanisms remain unclear. Here we addressed if mitochondria are involved in the cytotoxicity of the novel 1,4-dihydropyridine derivative VE-3N [ethyl 6-chloro-5-formyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate] towa...

This study presents the impact of carbon nanotubes (CNTs) on mitochondrial oxygen mass flux (Jm) under three experimental conditions. New experimental results and a new methodology are reported for the first time and they are based on CNT Raman spectra star graph transform (spectral moments) and perturbation theory. The experimental measures of Jm...

Saxitoxins (STXs) are potent neurotoxins that block voltage-gated channels in neurons and induce cytotoxicity. These toxins not only can generate reactive oxygen species but also can alter antioxidant levels, promoting oxidative stress. Under this pro-oxidant situation, the use of the antioxidant lipoic acid (LA) can represent a chemoprotective alt...

The current molecular docking study provided the Free Energy of Binding (FEB) for the interaction (nanotoxicity) between VDAC mitochondrial channels of three species (VDAC1-Mus musculus, VDAC1-Homo sapiens, VDAC2-Danio rerio) with SWCNT-H, SWCNT-OH, SWCNT-COOH carbon nanotubes. The general results showed that the FEB values were statistically more...

In the present study, different in vitro and electrochemical protocols were employed to determine the mitoprotective properties of carbon nanotubes family (pristine-CNT, oxidized-CNT) based on free radical scavenging ability against the most aggressive reactive oxygen species (ROS) as hydroxyl radical (·OH) formed by Fenton-Haber-Weiss reaction, wh...

The study of selective toxicity of carbon nanotubes (CNT) on mitochondria (CNT-mitotoxicity) is of major interest for future biomedical applications. In the current work, the mitochondrial oxygen consumption (E3) is measured under three experimental conditions by exposure to pristine and oxidized CNTs (hydroxylated and carboxylated). Respiratory fu...

Several 1,4-dihydropyridine derivatives overcome the multidrug resistance in tumors, but their intrinsic cytotoxic mechanisms remain unclear. Here we addressed if mitochondria are involved in the cytotoxicity of the novel 1,4-dihydropyridine derivative VE-3N [ethyl 6-chloro-5-formyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate] towa...

Saxitoxins (STXs) are potent neurotoxins that also induce cytotoxicity through reactive oxygen species (ROS) generation. Carbon nanotubes (CNTs) are nanomaterials (NM) that can promote the 'Trojan horse' effect, facilitating the entry of toxic molecules to cells when adsorbed to NM. The interaction of pristine single-walled (SWCNT) and carboxylated...

Interactions between the single walled carbon nanotube (SWCNT) family and a mitochondrial ADP/ATP carrier (ANT-1) were evaluated using constitutional (functional groups, number of carbon atoms, etc.) and electronic nanodescriptors defined by (n, m)-Hamada indexes (armchair, zig-zag and chiral). The Free Energy of Binding (FEB) was determined by mol...

Mitochondrial Permeability Transition Pore (MPTP) is involved in neurodegeneration, hepatotoxicity, cardiac necrosis, nervous and muscular dystrophies. We used different experimental protocols to determine the mitoprotective activity (%P) of different carbon nanotubes (CNT) against mitochondrial swelling in multiple boundary conditions (bj). The ex...

The ischemic stroke cascade is composed of several pathophysiological events, providing multiple targets for pharmacological intervention. JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido[2,3-b][1,5]benzodiazepine) is a novel hybrid molecule, in which a benzodiazepine portion is covalently linked to a dihydropyridine ring,...