(Heteroarylmethyl)benzoic Acids as a New Class of Bacterial Cystathionine γ-Lyase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modeling.

Antibiotic resistance is one of the most serious global health threats. Therefore, there is a need to develop antimicrobial agents with new mechanisms of action. Targeting of bacterial cystathionine γ-lyase (bCSE), an enzyme essential for bacterial survival, is a promising approach to overcome antibiotic resistance.

In Vitro Antioxidant and In Vivo Antigenotoxic Features of a Series of 61 Essential Oils and Quantitative Composition-Activity Relationships Modeled through Machine Learning Algorithms.

The antioxidant activity of essential oils (EOs) is an important and frequently studied property, yet it is not sufficiently understood in terms of the contribution of EOs mixtures' constituents and biological properties. In this study, a series of 61 commercial EOs were first evaluated as antioxidants in vitro, following as closely as possible the cellular pathways of reactive oxygen species (ROS) generation. Hence, EOs were assessed for the ability either to chelate metal ions, thus interfering with ROS generation within the respiratory chain, or to neutralize 2,2-diphenyl-1-picrylhydrazyl (DPPH) and lipid peroxide radicals (LOO), thereby halting lipid peroxidation, as well as to neutralize 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid cation radicals (ABTS) and hydroxyl radicals (OH), thereby preventing the ROS species from damaging DNA nucleotides.

Chemical Composition and Anti- Activity of Ehrh. Essential Oils Obtained by Different Distillation Processes.

A comparative study on essential oils extracted from Ehrh. from Italy is reported. Two extraction procedures were investigated: hydrodistillation and steam distillation, carried out as a continuous and fractionated procedure.

Molecular Docking Assessment of Cathinones as 5-HTR Ligands: Developing of Predictive Structure-Based Bioactive Conformations and Three-Dimensional Structure-Activity Relationships Models for Future Recognition of Abuse Drugs.

Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HTR, the enclosed study summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure-activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine.

Pyrimidine thioethers: A novel class of antidepressant agents, endowed with anxiolytic, performance enhancing and nootropic activity.

A series of new pyrimidine thioethers, recognized as the key intermediates in the synthesis of S-DABO antivirals, were prepared and evaluated both in vivo and in silico. The purpose of this evaluation was to find novel structural analogues of the known antihypoxic drug Isothiobarbamine endowed with improved pharmacological profile. The in vivo studies led to the identification of compounds 5c, 5e, and 5f endowed with antidepressant/anxiolytic, performance enhancing, and nootropic properties.

Synthesis and biological evaluation of new quinoline-4-carboxylic acid-chalcone hybrids as dihydroorotate dehydrogenase inhibitors.

Fourteen novel quinoline-4-carboxylic acid-chalcone hybrids were obtained via Claisen-Schmidt condensation and evaluated as potential human dihydroorotate dehydrogenase (hDHODH) inhibitors. The ketone precursor 2 was synthesized by the Pfitzinger reaction and used for further derivatization at position 3 of the quinoline ring for the first time. Six compounds showed better hDHODH inhibitory activity than the reference drug leflunomide, with IC values ranging from 0.

Chemical Composition of Various Plant Organs' Methanol Extracts Associated with Hepatoprotective and Antigenotoxic Features as well as Molecular Modeling Investigations.

This report summarizes the chemical composition analysis of L. flower, leaf, and stem methanol extracts (FME, LME, SME, respectively) as well as their hepatoprotective and antigenotoxic features and . Herein, Wistar rat liver intoxication with CCl resulted in the generation of trichloromethyl and trichloromethylperoxy radicals, causing lipid peroxidation within the hepatocyte membranes (viz.

Ligand-based and structure-based studies to develop predictive models for SARS-CoV-2 main protease inhibitors through the 3d-qsar.com portal.

The main protease (M) of SARS-Cov-2 is the essential enzyme for maturation of functional proteins implicated in viral replication and transcription. The peculiarity of its specific cleavage site joint with its high degree of conservation among all coronaviruses promote it as an attractive target to develop broad-spectrum inhibitors, with high selectivity and tolerable safety profile. Herein is reported a combination of three-dimensional quantitative structure-activity relationships (3-D QSAR) and comparative molecular binding energy (COMBINE) analysis to build robust and predictive ligand-based and structure-based statistical models, respectively.

Human Estrogen Receptor Alpha Antagonists, Part 3: 3-D Pharmacophore and 3-D QSAR Guided Brefeldin A Hit-to-Lead Optimization toward New Breast Cancer Suppressants.

The estrogen receptor α (ERα) is an important biological target mediating 17β-estradiol driven breast cancer (BC) development. Aiming to develop innovative drugs against BC, either wild-type or mutated ligand-ERα complexes were used as source data to build structure-based 3-D pharmacophore and 3-D QSAR models, afterward used as tools for the virtual screening of National Cancer Institute datasets and hit-to-lead optimization. The procedure identified Brefeldin A () as hit, then structurally optimized toward twelve new derivatives whose anticancer activity was confirmed both in vitro and in vivo.

Novel non-covalent LSD1 inhibitors endowed with anticancer effects in leukemia and solid tumor cellular models.

LSD1 is a histone lysine demethylase proposed as therapeutic target in cancer. Chemical modifications applied at C2, C4 and/or C7 positions of the quinazoline core of the previously reported dual LSD1/G9a inhibitor 1 led to a series of non-covalent, highly active, and selective LSD1 inhibitors (2-4 and 6-30) and to the dual LSD1/G9a inhibitor 5 that was more potent than 1 against LSD1. In THP-1 and MV4-11 leukemic cells, the most potent compounds (7, 8, and 29) showed antiproliferative effects at sub-micromolar level without significant toxicity at 1 μM in non-cancer AHH-1 cells.

Human estrogen receptor α antagonists, part 2: Synthesis driven by rational design, in vitro antiproliferative, and in vivo anticancer evaluation of innovative coumarin-related antiestrogens as breast cancer suppressants.

New twelve in silico designed coumarin-based ERα antagonists, namely 3DQ-1a to 3DQ-1е, were synthesized and confirmed as selective ERα antagonists, showing potencies ranging from single-digit nanomolar to picomolar. The hits were confirmed as selective estrogen receptor modulators and validated as antiproliferative agents using MCF-7 breast cancer cell lines exerting from picomolar to low nanomolar potency, at the same time showing no agonistic activity within endometrial cell lines. Their mechanism of action was inspected and revealed to be through the inhibition of the Raf-1/MAPK/ERK signal transduction pathway, preventing hormone-mediated gene expression on either genomic direct or genomic indirect level, and stopping the MCF-7 cells proliferation at G/G phase.

Human Estrogen Receptor α Antagonists. Part 1: 3-D QSAR-Driven Rational Design of Innovative Coumarin-Related Antiestrogens as Breast Cancer Suppressants through Structure-Based and Ligand-Based Studies.

The estrogen receptor α (ERα) represents a 17β-estradiol-inducible transcriptional regulator that initiates the RNA polymerase II-dependent transcriptional machinery, pointed for breast cancer (BC) development either genomic direct or genomic indirect (., tethered) pathway. To develop innovative ligands, structure-based (SB) three-dimensional (3-D) quantitative structure-activity relationship (QSAR) studies have been undertaken from structural data taken from partial agonists, mixed agonists/antagonists (selective estrogen receptor modulators (SERMs)), and full antagonists (selective ERα downregulators (SERDs)) correlated with either wild-type or mutated ERα receptors.

Low cytotoxic quinoline-4-carboxylic acids derived from vanillin precursors as potential human dihydroorotate dehydrogenase inhibitors.

Twenty novel 2-substituted quinoline-4-carboxylic acids bearing amide moiety were designed and synthesized by Doebner reaction. Human dihydroorotate dehydrogenase (hDHODH) was recognized as a biological target and all compounds were screened as potential hDHODH inhibitors in an enzyme inhibition assay. The prepared heterocycles were also evaluated for their cytotoxic effects on the healthy HaCaT cell line while lipophilic properties were considered on the basis of experimentally determined logD values at physiological pH.

Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies.

A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity.

Pyrazole Derivatives of Medically Relevant Phenolic Acids: Insight into Antioxidative and Anti-LOX Activity.

Background: From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds.

Objective: The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities.

Methods: Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids.

The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro.

Commercially available pesticides were examined as and acetylcholinesterase (AChE and AChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron.

Dicoumarol derivatives: Green synthesis and molecular modelling studies of their anti-LOX activity.

Dicoumarol derivatives were synthesized in the InCl catalyzed pseudo three-component reactions of 4-hydroxycoumarin with aromatic aldehydes in excellent yields. The reactions were performed in water under microwave irradiation. All synthesized compounds were characterized using NMR, IR, and UV-Vis spectroscopy, as well as with TD-DFT.

Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents.

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurally characterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemia cell lines and significantly lower cytotoxic effects against normal MRC-5 cells, indicating very high selectivity in their anticancer action. The compounds 6g, 6u and 6v activate apoptosis in K562 cells through the extrinsic and intrinsic apoptotic pathway.

16-membered macrolide antibiotics: a review.

The 16-membered macrolide antibiotics (e.g. tylosin A and josamycin) are mainly used in veterinary medicine, and are much less studied than their 14- and 15-membered erythromycin-based cousins.

Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition.

Mannich bases of 1,2,4-triazole-3-thione containing adamantane moiety: Synthesis, preliminary anticancer evaluation, and molecular modeling studies.

A series of 18 novel N-Mannich bases derived from 5-adamantyl-1,2,4-triazole-3-thione was synthesized and characterized using NMR spectroscopy and X-ray diffraction technique. All derivatives were evaluated for their anticancer potential against four human cancer cell lines. Several tested compounds exerted good cytotoxic activities on K562 and HL-60 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal fibroblasts MRC-5 compared to cancer cells.

Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney oxidative stress in rats: In vivo investigation and LC-MS analysis.

Filipendula ulmaria, known as meadowsweet, is a perennial herb found in wild and cultivated habitats in Europe and Asia. Usage of F. ulmaria in traditional medicine is based on diuretic, astringent, antirheumatic, and anti-inflammatory properties of this plant.

Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and antimicrobial agent.

The aim of this study was to investigate the antioxidant activity of the methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots (FHR) and their potential in different model systems, as well as antimicrobial activity. According to this, a number of assays were employed to evaluate the antioxidant and antimicrobial potential of F.