Molecular modeling and cytotoxic activity studies of oxirane-2-carboxylate derivatives.

In this study, five 3-aryloxirane-2-carboxylate derivatives were prepared, and the antiproliferative activities of molecules were screened in lung and colon cancer cell lines. The results showed that molecules had antiproliferative activity on cancerous cells with IC values under 100 µM. Furthermore, all of the molecules were found to have a much higher cytotoxic effect than cisplatin in colon cancer cells.

Computational exploration of acefylline derivatives as MAO-B inhibitors for Parkinson's disease: insights from molecular docking, DFT, ADMET, and molecular dynamics approaches.

Monoamine oxidase B (MAO-B) plays a pivotal role in the deamination process of monoamines, encompassing crucial neurotransmitters like dopamine and norepinephrine. The heightened interest in MAO-B inhibitors emerged after the revelation that this enzyme could potentially catalyze the formation of neurotoxic compounds from endogenous and exogenous sources. Computational screening methodologies serve as valuable tools in the quest for novel inhibitors, enhancing the efficiency of this pursuit.

Mitochondrial toxicity of selected natural compounds: assessment and molecular docking and dynamics simulation.

Boiss & Hausskn stands out for its rich bioactive constituents including prantschimgin (PRA), imperatorin (IMP), suberosin (SUB), adicardin (ADI), and oxypeucedanin hydrate (OPH) in the Apiaceae family. Although these molecules contribute to several biological activities, their mitochondrial toxicity were not illuminated in depth with the appropriate and models. Cell viability studies investigated the cytotoxic activities of molecules in HepG2 cells by replacing glucose with galactose due to Warburg effects.

Synthesis of Novel Cu(II), Co(II), Fe(II), and Ni(II) Hydrazone Metal Complexes as Potent Anticancer Agents: Spectroscopic, DFT, Molecular Docking, and MD Simulation Studies.

Metal complexes [FeL], [NiL]·HO, [CuL], and [CoL]·HO were formed by the ligand (, 4-fluoro-'-(2-hydroxybenzylidene)benzohydrazide) reacting with Fe(OAc), Ni(OAc)·4HO, Cu(OAc)·HO, and Co(OAc)·4HO. The produced compounds were characterized using a variety of methods, such as NMR, UV-vis, FT-IR, magnetic susceptibility, elemental analysis, and molar conductivity. The spectrum of the data indicates that the geometry of the complex molecular structures is octahedral with six coordination sites.

Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer's Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation.

Considering the complex pathogenesis of Alzheimer's disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide () and four corresponding hydrazide-hydrazones () were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating.

Targeting COVID-19 and varicocele by blocking inflammasome: Ligand-based virtual screening.

COVID-19 is a new generation of outbreaks that invade not only local emerging region, continental but also the whole globe. Varicocele on the other hand, is a testicular vascular disease that underlies 40 % of male infertility cases. Fortunately, the two diseases can be blocked through targeting one common target, NLRP3 inflammasome.

Exploring theophylline-1,2,4-triazole tethered -phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, validation, and insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against QB-928 and AB-274.

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches.

Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole - and benzofuran-1,2,4-triazole compounds - were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole - molecules.

Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole-1,2,4-Triazole-Based -Alkylated -Aryl Acetamides.

Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole-1,2,4-triazol-based -phenyl acetamide structural motifs - were synthesized and screened against the in vitro hepatocellular cancer Hep-G2 cell line. The MTT assay was applied to determine the anti-proliferative potential of novel indole-triazole compounds -, which displayed cytotoxicity potential as cell viabilities at 100 µg/mL concentration, by using ellipticine and doxorubicin as standard reference drugs.

Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2-benzimidazol-2-one derivatives.

Cancer is a global public health problem that affects millions each year. Novel anticancer drug candidates are in need to treat various cancers and to overcome the resistance that exists against drugs in use. Benzimidazole derivatives have been reported as anticancer agents.

Triiodothyronine positively regulates endoplasmic reticulum-associated degradation (ERAD) and promotes androgenic signaling in androgen-dependent prostate cancer cells.

Thyroid hormones (THs) play crucial roles in numerous physiological processes of nearly all mammalian tissues, including differentiation and metabolism. Deterioration of TH signaling has been associated with several pathologies, including cancer. The effect of highly active triiodothyronine (T3) has been investigated in many in vivo and in vitro cancer models.

Computational Insight into the Mechanism of Action of DNA Gyrase Inhibitors; Revealing a New Mechanism.

Background: Discovery of novel antimicrobial agents is in need to deal with antibiotic resistance. Elucidating the mechanism of action for established drugs contributes to this endeavor. DNA gyrase is a therapeutic target used in the design and development of new antibacterial agents.

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine-class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity.

Paraoxonase 1 (PON1) was purified 148.80-fold in 37.92% yield by hydrophobic interaction chromatography technique.

BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies.

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds . These bromobenzofuran-oxadiazole structural hybrids were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3β, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs , , and displayed the best anti-cancer potential and with the least cell viabilities (12.

Density functional modeling, and molecular docking with SARS-CoV-2 spike protein (Wuhan) and omicron S protein (variant) studies of new heterocyclic compounds including a pyrazoline nucleus.

Nowadays, different vaccines and antiviral drugs have been developed and their effectiveness has been proven against SARS-CoV-2. Pyrazoline derivatives are biologically active molecules and exhibit broad-spectrum biological activity properties. In this scope, four new molecules () including a pyrazoline core were synthesized in order to predict their antiviral properties theoretically.

Estrogens drive the endoplasmic reticulum-associated degradation and promote proto-oncogene c-Myc expression in prostate cancer cells by androgen receptor/estrogen receptor signaling.

The tumorigenic properties of prostate cancer are regulated by advanced hormonal regulation-mediated complex molecular signals. Therefore, characterizing the regulation of these signal transduction systems is crucial for understanding prostate cancer biology. Recent studies have shown that endoplasmic reticulum (ER)-localized protein quality control mechanisms, including ER-associated degradation (ERAD) and unfolded protein response (UPR) signaling contribute to prostate carcinogenesis and to the development of drug resistance.

1,25(OH) D induced vitamin D receptor signaling negatively regulates endoplasmic reticulum-associated degradation (ERAD) and androgen receptor signaling in human prostate cancer cells.

Steroid hormone signaling is critical in the tumor progression and the regulation of physiological mechanisms such as endoplasmic reticulum-associated degradation (ERAD) and unfolded protein response (UPR) in prostate cancer. 1,25(OH) D is an active metabolite of vitamin D classified as a steroid hormone. It exhibits anti-tumor effects, including angiogenesis and suppression of cell cycle progression.

Drug design of new therapeutic agents: molecular docking, molecular dynamics simulation, DFT and POM analyses of new Schiff base ligands and impact of substituents on bioactivity of their potential antifungal pharmacophore site.

Since Schiff base derivatives have a wide range of biological activities, novel Schiff base derivatives were designed and synthesized in satisfactory yields. H NMR, C NMR, IR, mass and elemental analysis were used to provide a complete structural characterization of the new synthesized Schiff bases (). The antiproliferative activity properties of compounds were tested against two human cancer cell lines including breast (MDA-MB-231) and colon (DLD-1).

Synthesis of novel carboxamide- and carbohydrazide-benzimidazoles as selective butyrylcholinesterase inhibitors.

Selectively inhibiting butyrylcholinesterase (BChE) is hypothesized to help in the management of Alzheimer's disease (AD). Several studies have determined a correlation between the increased activity of BChE and the onset of AD. An advantage of BChE over acetylcholinesterase inhibition is that absence of BChE activity does not lead to obvious physiological disturbance.

Fluorescence labelled XT5 modified nano-capsules enable highly sensitive myeloma cells detection.

Accurate diagnosis of cancer cells in early stages plays an important role in reliable therapeutic strategies. In this study, we aimed to develop fluorescence-conjugated polymer carrying nanocapsules (NCs) which is highly selective for myeloma cancer cells. To gain specific targeting properties, NCs, XT5 molecules (a benzamide derivative) which shows high affinity properties against protease-activated receptor-1 (PAR1), that overexpressed in myeloma cancer cells, was used.

Three dimensional structure prediction of panomycocin, a novel Exo-β-1,3-glucanase isolated from Wickerhamomyces anomalus NCYC 434 and the computational site-directed mutagenesis studies to enhance its thermal stability for therapeutic applications.

Panomycocin is a naturally produced potent antimycotic/antifungal protein secreted by the yeast Wickerhamomyces anomalus NCYC 434 with an exo-β-1,3-glucanase activity. In this study the three dimensional structure of panomycocin was predicted and the computational site-directed mutagenesis was performed to enhance its thermal stability in liquid formulations over the body temperature for topical therapeutic applications. Homology modeling was performed with MODELLER and I-TASSER.

Homology modeling in drug discovery: Overview, current applications, and future perspectives.

Homology modeling is one of the computational structure prediction methods that are used to determine protein 3D structure from its amino acid sequence. It is considered to be the most accurate of the computational structure prediction methods. It consists of multiple steps that are straightforward and easy to apply.