A5005571764- Computational Drug Discovery Methods
- Drug Solubulity and Delivery Systems
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Chemistry and Chemical Engineering
- Fullerene Chemistry and Applications
- Nanoparticle-Based Drug Delivery
- HIV-related health complications and treatments
- Receptor Mechanisms and Signaling
- Bioactive Compounds and Antitumor Agents
- Machine Learning in Materials Science
- Free Radicals and Antioxidants
- Analytical Chemistry and Chromatography
- Tryptophan and brain disorders
- Phytochemicals and Antioxidant Activities
- NF-κB Signaling Pathways
- Pharmacological Effects of Natural Compounds
- Protein purification and stability
- Spectroscopy and Quantum Chemical Studies
- Inflammatory mediators and NSAID effects
- Skin Protection and Aging
- Protein Structure and Dynamics
- Neuropeptides and Animal Physiology
- Nanoparticles: synthesis and applications
- Chromatography in Natural Products
National Hellenic Research Foundation
2011-2023
National and Kapodistrian University of Athens
2011-2023
NovaMechanics (Cyprus)
2016-2018
The emergence of HIV-1 drug-resistant mutations is the major problem against AIDS treatment. We employed molecular dynamics (MD) calculations and free energy (MM-PBSA thermodynamic integration) analyses on wild-type (WT) mutated protease (HIV-1 PR) complexes with darunavir, amprenavir, indinavir, saquinavir to clarify mechanism resistance due I50V flap mutation. Conformational analysis showed that flaps are increasingly flexible in complexes. In WT, stabilization PR structure achieved via...
Cyclodextrins (CDs) are a well-known class of supermolecules that have been widely used to protect drugs against conjugation and metabolic inactivation as well enhance the aqueous solubility hence ameliorate oral bioavailability sparingly soluble drug molecules. The hepatoprotectant silibinin can be incorporated into CDs, here we elucidate interaction between host at molecular level. complexation product with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) is characterized by Differential Scanning...
We present an in silico drug discovery pipeline developed and applied for the identification virtual screening of small-molecule Protein-Protein Interaction (PPI) compounds that act as dual inhibitors TNF RANKL through trimerization interface. The cheminformatics part was by combining structure-based with ligand-based modeling using largest available set known literature (2481 small molecules). To facilitate screening, consensus predictive model made freely at:...
A great challenge toward Acquired Immunodeficiency Syndrome (AIDS) treatment is to combat the HIV-1 virus. The major problem of drug resistance has kept virus one step ahead medical community, and call for more effective drugs remains as urgent ever. Saquinavir, first inhibitor against protease, offers most extensive clinical data regarding mutations. In this work, we examine L10I, G48V, L63P, A71V, G73S, V82A, I84V single mutant PR strains in complexes with saquinavir elucidate...
Human immunodeficiency virus type 1 protease (HIV-1 PR) and renin are primary targets toward AIDS hypertension therapies, respectively. Molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) free-energy calculations inhibition assays for canagliflozin, an antidiabetic agent verified its effective binding to both proteins (ΔGpred = −9.1 kcal mol–1 canagliflozin–renin; Ki,exp= 628 nM canagliflozin–HIV-1 PR). Moreover, drugs aliskiren (a inhibitor) darunavir (an HIV-1 PR showed high...
It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which turn upregulates β-secretase (BACE-1) expression levels, thereby propagating increasing injury. A series resveratrol derivatives, known to be inhibitors stress-induced cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory activity derivatives was...
Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the main targets toward AIDS therapy. We have selected potent drug darunavir and a weak inhibitor (fullerene analog) as HIV-1 PR substrates to compare protease's conformational features upon binding. Molecular dynamics (MD), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), quantum-mechanical (QM) calculations indicated importance stability flaps effective binding: may induce flexibility flaps, which convert...
Opioid G protein-coupled receptors (GPCRs) have been implicated in modulating pain, addiction, psychotomimesis, mood and memory, among other functions. We employed the recently reported crystal structure of human κ-opioid receptor (κ-OR) performed molecular dynamics (MD), free energy, ab initio calculations to elucidate binding mechanism complexes with antagonist JDTic agonist SalA. The two systems were modeled water DPPC lipid bilayers, order investigate effect membrane upon conformational...
Human serum albumin (HSA) is the most abundant blood plasma protein, which transports fatty acids, hormones, and drugs. We consider nanoparticle-HSA interactions by investigating binding of HSA with three fullerene analogs. Long MD simulations, quantum mechanical (fragment molecular orbital, energy decomposition analysis, atoms-in-molecules), free methods elucidated mechanism in these complexes. Such a systematic study valuable due to lack comprehensive theoretical approaches date. The main...
Renin–angiotensin aldosterone system inhibitors are for a long time extensively used the treatment of cardiovascular and renal diseases. AT1 receptor blockers (ARBs or sartans) act as antihypertensive drugs by blocking octapeptide hormone Angiotensin II to stimulate receptors. The drug candesartan (CAN) is active metabolite cilexetil (Atacand, CC). Complexes with 2-hydroxylpropyl-β-cyclodextrin (2-HP-β-CD) were characterized using high-resolution electrospray ionization mass spectrometry...
An in silico drug discovery pipeline for the virtual screening of plant-origin natural products (NPs) was developed to explore new direct inhibitors TNF and its close relative receptor activator nuclear factor kappa-B ligand (RANKL), both representing attractive therapeutic targets many chronic inflammatory conditions. Direct inhibition through identification potent small molecules is a highly desired goal; however, it often hampered by severe limitations. Our approach yielded priority list...
Mutations in the human immunodeficiency virus (HIV) enable replication even when appropriate antiretroviral therapy is followed, thus leading to emergence of drug resistance. In a previous work, we systematically examined seven single mutations that are associated with saquinavir (SQV) resistance HIV-1 protease (Tzoupis, H.; Leonis, G.; Mavromoustakos, T.; Papadopoulos, M. G. J. Chem. Theory Comput. 2013, 9, 1754–1764). Herein, extend our analysis, which includes double (G48V-V82A,...
There is no treatment, without side effects, efficiently preventing or curing skin burns, caused by radiotherapy. A new experimental topical treatment protocol was assessed in mice receiving orthovoltage X-rays at an equivalent dose to that applied human breast cancer patients conventional radiotherapy.SKH-HR2 female hairless were irradiated on their dorsum with a total of 4,300 cGy during 1-month period (20 fractions). The group received combination 3 products, oil-in-water cream, gel...
Losartan potassium salt (LSR) is a well-known antihypertensive drug with proven beneficial effects on human health. Its formulation the non-toxic 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) could improve its pharmacological profile. Thus, molecular interactions are studied using combination of Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) and Molecular Dynamics (MD). First, complexation shown through as lyophilization provided distinct thermal properties in...
Abstract Aliskiren is the first orally active, direct renin inhibitor to be approved for treatment of hypertension. Its structure elucidation and conformational analysis were explored using 1D 2D NMR spectroscopy, as well random search molecular dynamics (MD) simulations. For time, MD calculations have also been performed aliskiren at receptor site, in order reveal its basis action. It suggested that binds an extended conformation involved several stabilizing hydrogen bonding interactions...
The new molecule 4-[(2S)-2-(1H-imidazol-1-ylmethyl)-5-oxotetrahydro-1H-pyrrol-1-yl]methylbenzenecarboxylic acid (MMK16) was found to have promising anti-inflammatory activity. This biological behavior of MMK16 triggered our interest study its binding affinity using NMR spectroscopy in LOX and docking molecular dynamics (MD) properties COX enzymes. present studies not only rationalize the obtained results since all three receptors shows high scoring but also make it a potential dual...
(1)H NMR Saturation Transfer Difference (STD) experiments were applied to study the binding of aspirin and an anti-inflammatory complex Cu(I), namely [Cu(tpp)(pmt)](2) [pmt = 2-mercaptopyrimidine), synthesized in attempt develop novel metallotherapeutic molecules. While showed only very weak binding, clearly favored LOX-1. In silico docking LOX-1 that does weakly bind LOX-1, while binds with high affinity. addition, molecular dynamics (MD) simulations via hydrogen bonding (HB), allosteric...