Furopyridine Derivatives as Potent Inhibitors of the Wild Type, L858R/T790M, and L858R/T790M/C797S EGFR.

The treatment of patients with nonsmall cell lung cancer (NSCLC) using epidermal growth factor receptor (EGFR) inhibitors is complicated by drug-sensitive activating L858R/T790M and L858R/T790M/C797S mutations. To overcome drug resistance, a series of furopyridine (PD) compounds were virtually screened to identify potent EGFR inhibitors using molecular docking and molecular dynamics (MD) simulations based on the solvated interaction energy (SIE) method. Several PD compounds identified from virtual screening demonstrated the potential to suppress both wild-type and mutant forms of EGFR, with IC values in the nanomolar range.

Synthesis and Rearrangement of New 1,3-Diamino-2,7-naphthyridines and 1-Amino-3-oxo-2,7-naphthyridines.

Herein we describe the synthesis and rearrangement of 1,3-diamino-2,7-naphthyridines and 1-amino-3-oxo-2,7-naphthyridines. In the case of 1,3-diamino-2,7-naphthyridines, it was found that the rearrangement reaction was influenced by both the substituent at the 7th position of the 2,7-naphthyridine ring and by the nature of the cyclic amine at the 1st position. The influence was mainly steric.

COMPREHENSIVE STUDY OF ANTIOXIDANT ACTIVITY OF OXALIC ACID DIAMIDE DERIVATIVES AND THEIR EFFECT ON THE CONCENTRATION OF MALONIC DIALDEHYDE IN THE BRAIN AND LIVER TISSUES OF WHITE RATS.

Unlabelled: The wide range of chemical structures of antioxidants provides opportunities for individual selection of the most suitable compounds, taking into account the unique needs and characteristics of the body. Synthetic antioxidants can be specially designed with certain characteristics, which helps to create more effective and stable compounds. The aim of this work was to conduct a series of studies to identify the antioxidant activity of newly synthesized compounds of a number of oxalic acid diamides based on 3,4-dimethoxyphenylcyclopentylamine N1 ((1-3,4-dimethoxyphenyl)methyl)-N2-(2-methoxyphenyl)oxalamide on the content of malondialdehyde (MDA) in the brain and liver tissues of white rats (in vivo, in vitro), as well as to determine their potential pharmacological properties that correspond to Lipinsky's "Rule of Five" (in silico).

New triazole-based hybrids as neurotropic agents.

Herein, we describe the synthesis of new hybrids linked to 1,2,3- and 1,2,4-triazole units. Hybrids connected to a 1,2,3-triazole ring were synthesized using the well-known click reaction. The synthesis of the 1,2,4-triazole-based hybrids was carried out using 2-[(4-cyano-1-methyl(2-furyl)-5,6,7,8-tetrahydroisoquinolin-3-yl)oxy]acetohydrazides as starting compounds.

Synthesis and Psychotropic Properties of Novel Condensed Triazines for Drug Discovery.

The exploration of heterocyclic compounds and their fused analogs, featuring key pharmacophore fragments like pyridine, thiophene, pyrimidine, and triazine rings, is pivotal in medicinal chemistry. These compounds possess a wide array of biological activities, making them an intriguing area of study. The quest for new neurotropic drugs among derivatives of these heterocycles with pharmacophore groups remains a significant research challenge.

THE IMPACT OF DIAMIDE DERIVATIVES OF OXALIC ACID ON FREE RADICAL LIPID OXIDATION IN WHITE RAT BRAIN AND LIVER.

Antioxidants are widely used in medicine due to their ability to bind free radicals - active biomolecules that destroy the genetic apparatus of cells and the structure of their membranes, which makes it possible to reduce the intensity of oxidative processes in the body. In a living organism, free radicals are involved in various processes, but their activity is controlled by antioxidants. The purpose of this work was to conduct a series of studies to identify the antioxidant activity of new synthesized compounds of a series of oxalic acid diamides in the brain and liver tissue of white rats in vivo and in vitro experiments, as well as to determine their potential pharmacological properties.

Phthalazine Sulfonamide Derivatives as Carbonic Anhydrase Inhibitors. Synthesis, Biological and in silico Evaluation.

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several biological processes. They show a wide diversity in tissue distribution and their subcellular localization. Twenty-two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms: hCA I, hCA II, hCA IX, and hCA XII.

The Preparation of Silver and Gold Nanoparticles in Hyaluronic Acid and the Influence of Low-Pressure Plasma Treatment on Their Physicochemical and Microbiological Properties.

Nanometals constitute a rapidly growing area of research within nanotechnology. Nanosilver and nanogold exhibit significant antimicrobial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anticancer properties. The size and shape of nanoparticles are critical for determining their antimicrobial activity.

Revisiting the influence of pH on J and chemical shifts of glycine and alanine short oligopeptides.

The pH dependence of several NMR parameters of glycine and alanine short oligopeptides has been reported previously in different studies. Here we have thoroughly examined, summarized and demonstrated the dependences of H, C and N chemical shifts and protonation states of amino acids using two-dimensional NMR experiments. Nevertheless, J one bond spin-spin coupling constants are more informative and convenient for determination of the position and protonation state of glycine and alanine residue in the oligopeptide chain.

Predicting Pt NMR Chemical Shifts in Water-Soluble Inorganic/Organometallic Complexes with a Fast and Simple Protocol Combining Semiempirical Modeling and Machine Learning.

Water-soluble Pt complexes are the key components in medicinal chemistry and catalysis. The well-known cisplatin family of anticancer drugs and industrial hydrosylilation catalysts are two leading examples. On the molecular level, the activity mechanisms of such complexes mostly involve changes in the Pt coordination sphere.

New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking.

The synthesis of new original bicyclic pyridine-based hybrids linked to the 1,2,3-triazole unit was described via a click reaction. The anticonvulsant activity and some psychotropic properties of the new compounds were evaluated. The biological assays demonstrated that some of the studied compounds showed high anticonvulsant and psychotropic properties.

Oxidative stress and histopathological changes in several organs of mice injected with biogenic silver nanoparticles.

The widespread use of silver nanoparticles (AgNPs) requires a study of their safety. The aim of the present study was to assess the levels of oxidative stress markers and histopathological changes in the experimental model of sarcoma S-180 of outbred mice caused by biogenic AgNPs. AgNPs were synthesized using 50% ethanol extract of leaves that was standardized for rosmarinic acid content.

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents.

Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway.

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4',5']pyrido[3',2':4,5]thieno[3,2-]pyrimidines on the Basis of pyrano[3,4-]pyridines.

Background: Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem.

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds.

In this paper we describe an efficient method for the synthesis of new heterocyclic systems: furo[2,3-]-2,7-naphthyridines , as well as a new method for the preparation of 1,3-diamino-2,7-naphthyridines . For the first time, a Smiles rearrangement was carried out in the 2,7-naphthyridine series, thus gaining the opportunity to synthesize 1-amino-3-oxo-2,7-naphthyridines , which are the starting compounds for obtaining furo[2,3-]-2,7-naphthyridines. The cyclization of alkoxyacetamides proceeds via two different processes: the expected formation of furo[2,3-]-2,7-naphthyridines and the 'unexpected' formation of 1,3-diamino-2,7-naphthyridines ( a Smiles type rearrangement).

Synthesis of isomeric 4-(-methyltetrazolylamino)-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehydes and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde based on tandem thiol-Michael and (aza)-Morita-Baylis-Hillman reactions and an study of the activity of the obtained compounds against influenza virus.

Unlabelled: 3-{[(1-Methyl-1-tetrazol-5-yl)imino]methyl}quinoline-2-thiol and 3-{[(2-methyl-2-tetrazol-5-yl)imino]methyl}quinoline-2-thiol were synthesized. The sequence of the thiol-Michael reaction and the (aza)-Morita-Baylis-Hillman reaction yielded 4-[(1-methyl-1-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde, 4-[(2-methyl-2-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]-quinoline-3-carbaldehyde, and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde. Cytotoxicity and antiviral activity against the A/Puerto Rico/8/34 (H1N1) influenza virus strain in MDCK cell culture were determined for the obtained compounds.

Long range deuterium isotope effects on C NMR chemical shifts of 2-alkanones in CDOD solutions of imidazolium acetate ionic liquids.

Deuterium isotope substitution in one part of a molecule could produce a significant effect on chemical shifts of neighbouring nuclei as well as on nuclei, located far from the site of replacement. To estimate how far this influence could extend the reaction of proton-deuterium exchange of several 2-alkanones in deuterated methanol solutions of 1-methyl 3-ethyl imidazolium acetate ionic liquid (IL) was studied in detail using C NMR spectroscopy. Deuteration occurs in alkyl groups of 2-alkanones neighboring the ketonic group keto-enol tautomerization catalyzed by IL.

Light-driven photoswitching of quinazoline analogues of combretastatin A-4 as an effective approach for targeting skin cancer cells.

A novel quinazoline series of photoswitchable combretastatin A-4 (CA-4) analogues were synthesized and their photochemical properties and antiproliferative activity against A431 epidermoid carcinoma cells were studied. It was found that quinazoline analogues, in contrast to the majority of the known CA-4, exhibit high antiproliferative activity in the -form as well. Photoswitching of the -form to the -form resulted in a multiple (9-fold) increase in antiproliferative activity.

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-]pyrrolo[1,2-]pyrimidines, Pyridofuro[3,2-]pyrido[1,2-]pyrimidines and Pyridofuro[3',2':4,5]pyrimido[1,2-]azepines.

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore.

Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity.

Objectives: Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule.

Methods: The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide.

Sexual Dimorphism in Alternative Metabolic Pathways of L-Arginine in Circulating Leukocytes in Young People with Type 1 Diabetes Mellitus.

: Sexual dimorphism in specific biochemical pathways and immune response, underlies the heterogeneity of type 1 diabetes mellitus (T1DM) and affects the outcome of immunotherapy. Arginase and nitric oxide (NO) synthase (NOS) metabolize L-arginine and play opposite roles in the immune response and autoimmune processes. We hypothesized that the above mentioned enzymes can be involved in sex and age differences in T1DM and its treatment.

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity.

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity.