A Universal Method for the Synthesis of new Heterocyclic Systems: Pyrimido[2,1-f][1,2,4]triazines.

The synthesis of pyrimido[2,1-f][1,2,4]triazines was performed in four steps. Compounds obtained by acylation of the starting amino esters of thieno[2,3-b]pyridines were reacted with various amines. The resulting amino derivatives underwent cyclization in the presence of hydrazine hydrate leading to new aminomethyl derivatives of thieno[3,2-d]pyrimidines.

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.

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.

Anti-inflammatory action of new hybrid -acyl-[1,2]dithiolo-[3,4-]quinoline-1-thione.

Most of pharmaceutical agents display a number of biological activities. It is obvious that testing even one compound for thousands of biological activities is not practically possible. A computer-aided prediction is therefore the method of choice in this case to select the most promising bioassays for particular compounds.

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.

Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation.

Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types.

Discovery of furopyridine-based compounds as novel inhibitors of Janus kinase 2: In silico and in vitro studies.

Janus kinase 2 (JAK2), one of the JAK isoforms participating in a JAK/STAT signaling cascade, has been considered a potential clinical target owing to its critical role in physiological processes involved in cell growth, survival, development, and differentiation of various cell types, especially immune and hematopoietic cells. Substantial studies have proven that the inhibition of this target could disrupt the JAK/STAT pathway and provide therapeutic outcomes for cancer, immune disorders, inflammation, and COVID-19. Herein, we performed docking-based virtual screening of 63 in-house furopyridine-based compounds and verified the first-round screened compounds by in vitro enzyme- and cell-based assays.

A Study of the Peculiarities of the Formation of a Hybrid Interface Based on Polydopamine between Dental Tissues and Dental Composites, Using IR and Raman Microspectroscopy, at the Submicron Level.

The creation of buffer (hybrid) layers that provide improved adhesion to two heterogeneous materials is a promising and high-priority research area in the field of dental materials science. In our work, using FTIR and Raman microspectroscopy at the submicron level in a system of dental composites/intact dental enamel, we assessed the molecular features of formation and chemically visualized the hybrid interface formed on the basis of a nature-like adhesive, polydopamine (PDA). It is shown that a homogeneous bioinspired PDA-hybrid interface with an increased content of O-Ca-O bonds can be created using traditional methods of dental tissue pretreatment (diamond micro drilling, acid etching), as well as the subsequent alkalinization procedure and the developed synthesis technology.

Substituted furan sulfonamides as carbonic anhydrase inhibitors: Synthesis, biological and in silico studies.

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several of biological processes, such as respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show wide diversity in tissue distribution and in their subcellular localization. Fifteen novel furyl sulfonamides were designed, synthesized and evaluated against four human isoforms: hCA I, hCA II, hCA IV and hCA IX.

Functionally substituted 2-aminothiazoles as antimicrobial agents: in vitro and in silico evaluation.

Nine new functionally substituted derivatives of 2-aminothiazole were evaluated for antimicrobial activity using microdilution method against the panel of eight bacterial and eight fungal strains. Evaluation of antibacterial activity revealed that compounds are potent antibacterial agents, more active than ampicillin and streptomycin except of some compounds against and . The best compound appeared to be compound 8.

Discovery of Novel EGFR Inhibitor Targeting Wild-Type and Mutant Forms of EGFR: In Silico and In Vitro Study.

Targeting L858R/T790M and L858R/T790M/C797S mutant EGFR is a critical challenge in developing EGFR tyrosine kinase inhibitors to overcome drug resistance in non-small cell lung cancer (NSCLC). The discovery of next-generation EGFR tyrosine kinase inhibitors (TKIs) is therefore necessary. To this end, a series of furopyridine derivatives were evaluated for their EGFR-based inhibition and antiproliferative activities using computational and biological approaches.

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.

Synthesis, Biological and In Silico Studies of Griseofulvin and Usnic Acid Sulfonamide Derivatives as Fungal, Bacterial and Human Carbonic Anhydrase Inhibitors.

Carbonic anhydrases (CAs, EC 4.2.1.

-Derivatives of ()-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1-indole-2-carboxylates as Antimicrobial Agents-In Silico and In Vitro Evaluation.

Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new ()-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1-indole-2-carboxylate derivatives. All tested compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin as well as streptomycin by 10-50 fold.

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents.

In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity.

Synthesis and Antimicrobial Activity of New Heteroaryl(aryl) Thiazole Derivatives Molecular Docking Studies.

Herein, we report the design, synthesis, and evaluation of the antimicrobial activity of new heteroaryl (aryl) thiazole derivatives. The design was based on a molecular hybridization approach. The in vitro evaluation revealed that these compounds demonstrated moderate antibacterial activity.

Imidazole Derivative As a Novel Translation Inhibitor.

Searching for novel compounds with antibiotic activity and understanding their mechanism of action is extremely important. The ribosome is one of the main targets for antibiotics in bacterial cells. Even if the molecule does not suit the clinical application for whatever reasons, an investigation of its mechanism of action can deepen our understanding of the ribosome function.

Combined Cytotoxic Effect of Inhibitors of Proteostasis on Human Colon Cancer Cells.

Despite significant progress in the diagnosis and treatment of colorectal cancer, drug resistance continues to be a major limitation of therapy. In this regard, studies aimed at creating combination therapy are gaining popularity. One of the most promising adjuvants are inhibitors of the proteostasis system, chaperone machinery, and autophagy.

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.

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).

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies.

Carbonic anhydrases (CAs, EC 4.2.1.

Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.

Background: Infectious diseases represent a significant global strain on public health security and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains.

Methods: Compounds were synthesized using the classical organic chemistry methods.

Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors.

A series of benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with several bulky moieties has been obtained by original procedures. The new derivatives were investigated for the inhibition of four physiologically crucial human carbonic anhydrase (hCA, EC 4.2.