Synthesis and effect of 4-acetylphenylamine-based imidazole derivatives on migration and growth of 3D cultures of breast, prostate and brain cancer cells.

In this study, we have synthesized novel 4-acetophenone moiety-bearing functionalized imidazole derivatives containing S-, and N-ethyl substituents and evaluated their anticancer activity. Their anticancer activity was studied against human breast carcinoma (MDA-MB-231), human prostate carcinoma (PPC-1), and human glioblastoma (U-87). Compounds 4, 9, 14, and 22 were identified as the most promising anticancer agents from a series of imidazole derivatives.

Identification of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Anticancer Candidates with Promising Antioxidant Properties.

Various cancer-associated morbidities remain a growing global health challenge, resulting in a significant burden on healthcare systems worldwide due to high mortality rates and a frequent lack of novel therapeutic options for advanced and localized disease. Reactive oxygen species (ROS) play an important role in cancer pathogenesis and response to chemotherapeutics; therefore, it is crucial to develop novel compounds with both antioxidant and anticancer activity. In this study, a series of previously reported 3-((4-hydroxyphenyl)amino)propanoic acid derivatives (compounds -) were evaluated for their anticancer and antioxidant activities.

Screening of Small-Molecule Libraries Using SARS-CoV-2-Derived Sequences Identifies Novel Furin Inhibitors.

SARS-CoV-2 is the pathogen responsible for the most recent global pandemic, which has claimed hundreds of thousands of victims worldwide. Despite remarkable efforts to develop an effective vaccine, concerns have been raised about the actual protection against novel variants. Thus, researchers are eager to identify alternative strategies to fight against this pathogen.

Exploring the potential of bis(thiazol-5-yl)phenylmethane derivatives as novel candidates against genetically defined multidrug-resistant Staphylococcus aureus.

Antimicrobial resistance (AMR) represents an alarming global challenge to public health. Infections caused by multidrug-resistant Staphylococcus aureus (S. aureus) pose an emerging global threat.

Synthesis of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Promising Scaffolds for the Development of Antimicrobial Candidates Targeting Multidrug-Resistant Bacterial and Fungal Pathogens.

Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions.

The Effect of 4-(Dimethylamino)phenyl-5-oxopyrrolidines on Breast and Pancreatic Cancer Cell Colony Formation, Migration, and Growth of Tumor Spheroids.

A series of hydrazones, azoles, and azines bearing a 4-dimethylaminophenyl-5-oxopyrrolidine scaffold was synthesized. Their cytotoxic effect against human pancreatic carcinoma Panc-1 and triple-negative breast cancer MDA-MB-231 cell lines was established by MTT assay. Pyrrolidinone derivatives and , with incorporated 5-chloro and 5-methylbenzimidazole fragments; hydrazone bearing a 5-nitrothien-2-yl substitution; and hydrazone with a naphth-1-yl fragment in the structure significantly decreased the viability of both cancer cell lines.

Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors.

The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL) and main protease (M) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL. The hit compounds structurally belonged to two classes of small molecules: thiazole derivatives and symmetrical disulfide compounds.

Synthesis of 1-(2-Hydroxyphenyl)- and (3,5-Dichloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives as Promising Scaffolds for the Development of Novel Antimicrobial and Anticancer Agents.

Increasing antimicrobial resistance among Gram-positive pathogens and pathogenic fungi remains one of the major public healthcare threats. Therefore, novel antimicrobial candidates and scaffolds are critically needed to overcome resistance in Gram-positive pathogens and drug-resistant fungal pathogens. In this study, we explored 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid and its 3,5-dichloro-2-hydroxyphenyl analogue for their in vitro antimicrobial activity against multidrug-resistant pathogens.

Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Complex.

Infections caused by drug-resistant (DR) () complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant strains and compared their antimycobacterial activity using BCG and H37Ra.

Synthesis of novel sulphamethoxazole derivatives and exploration of their anticancer and antimicrobial properties.

A series of new derivatives based on sulfamethoxazole were designed and synthesized in this study. The structures of the new compounds were confirmed based on a comprehensive characterization of spectral data by applied IR and 1H as well as 13C NMR spectroscopy. The prepared compounds were tested for their anticancer and antimicrobial properties.

Synthesis and Development of -2,5-Dimethylphenylthioureido Acid Derivatives as Scaffolds for New Antimicrobial Candidates Targeting Multidrug-Resistant Gram-Positive Pathogens.

The growing antimicrobial resistance to last-line antimicrobials among Gram-positive pathogens remains a major healthcare emergency worldwide. Therefore, the search for new small molecules targeting multidrug-resistant pathogens remains of great importance. In this paper, we report the synthesis and in vitro antimicrobial activity characterisation of novel thiazole derivatives using representative Gram-negative and Gram-positive strains, including tedizolid/linezolid-resistant as well as emerging fungal pathogens.

Synthesis and Biological Activity Characterization of Novel 5-Oxopyrrolidine Derivatives with Promising Anticancer and Antimicrobial Activity.

The 1-(4-acetamidophenyl)-5-oxopyrrolidine carboxylic acid was applied for synthesizing derivatives bearing azole, diazole, and hydrazone moieties in the molecule. Modification of an acetamide fragment to the free amino group afforded compounds with two functional groups, which enabled to provide a series of 4-substituted-1-(4-substituted phenyl)pyrrolidine-2-ones. The resulted compounds and - were subjected to the in vitro anticancer and antimicrobial activity determination.

Synthesis of Novel Aminothiazole Derivatives as Promising Antiviral, Antioxidant and Antibacterial Candidates.

It is well-known that thiazole derivatives are usually found in lead structures, which demonstrate a wide range of pharmacological effects. The aim of this research was to explore the antiviral, antioxidant, and antibacterial activities of novel, substituted thiazole compounds and to find potential agents that could have biological activities in one single biomolecule. A series of novel aminothiazoles were synthesized, and their biological activity was characterized.

Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-associated mortalities worldwide. Therefore, it is crucial to develop a novel therapeutic option targeting localized and metastatic NSCLC. In this paper, we describe the synthesis and biological activity characterization of naphthoquinone derivatives bearing selective anticancer activity to NSCLC via a COX-2 mediated pathway.

Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases.

A series of novel benzenesulfonamide derivatives were synthesized bearing - β,γ-amino acid or - β-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals.

Synthesis of Novel Thiazole Derivatives Bearing β-Amino Acid and Aromatic Moieties as Promising Scaffolds for the Development of New Antibacterial and Antifungal Candidates Targeting Multidrug-Resistant Pathogens.

Rapidly growing antimicrobial resistance among clinically important bacterial and fungal pathogens accounts for high morbidity and mortality worldwide. Therefore, it is critical to look for new small molecules targeting multidrug-resistant pathogens. Herein, in this paper we report a synthesis, ADME properties, and in vitro antimicrobial activity characterization of novel thiazole derivatives bearing β-amino acid, azole, and aromatic moieties.

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles.

Evaluation of N-aryl-β-alanine derivatives as anticancer agents in triple-negative breast cancer and glioblastoma in vitro models.

Synthesis of β-amino acid derivatives containing hydrazone and azole moieties is described. For this purpose, the appropriate hydrazide was treated with aromatic aldehydes, ketones and phenyl iso(thio)cyanates to obtain the desired outcome. The synthesized target compounds were evaluated for their anticancer properties.

Novel -Substituted Amino Acid Hydrazone-Isatin Derivatives: Synthesis, Antioxidant Activity, and Anticancer Activity in 2D and 3D Models .

A series of novel mono and bishydrazones each bearing a 2-oxindole moiety along with substituted phenylaminopropanamide, pyrrolidin-2-one, benzimidazole, diphenylmethane, or diphenylamine fragments were synthesized, and their anticancer activities were tested by MTT assay against human melanoma A375 and colon adenocarcinoma HT-29 cell lines. In general, the synthesized compounds were more cytotoxic against HT-29 than A375. 3-((4-Methoxyphenyl)(3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)propyl)amino)-'-(2-oxoindolin-3-ylidene)propanehydrazide and (',‴)-1,1'-(methylenebis(4,1-phenylene))bis(5-oxo-'-(2-oxoindolin-3-ylidene)pyrrolidine-3-carbohydrazide) were identified as the most active compounds against HT-29 in 2D and 3D cell cultures.

Synthesis and Antibacterial Activity of New Azole, Diazole and Triazole Derivatives Based on -Aminobenzoic Acid.

The aminobenzoic acid was applied for the synthesis of substituted 1-phenyl-5-oxopyrrolidine derivatives containing benzimidazole, azole, oxadiazole, triazole, dihydrazone, and dithiosemicarbazide moieties in the structure. All the obtained compounds were evaluated for their in vitro antimicrobial activity against , , , , and by using MIC and MBC assays. This study showed a good bactericidal activity of -amino acid and benzimidazoles derivatives.

Synthesis, ADMET Properties, and In Vitro Antimicrobial and Antibiofilm Activity of 5-Nitro-2-thiophenecarbaldehyde N-((E)-(5-Nitrothienyl)methylidene)hydrazone (KTU-286) against with Defined Resistance Mechanisms.

The emergence of drug-resistant is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant strains with genetically defined resistance mechanisms.

Antioxidant and Anticancer Activity of Novel Derivatives of 3-[(4-Methoxyphenyl)amino]propane-hydrazide.

Series of novel 3-[(4-methoxyphenyl)amino]propanehydrazide derivatives bearing semicarbazide, thiosemicarbazide, thiadiazole, triazolone, triazolethione, thiophenyltriazole, furan, thiophene, naphthalene, pyrrole, isoindoline-1,3-dione, oxindole, etc. moieties were synthesized and their molecular structures were confirmed by IR, H-, C-NMR spectroscopy and mass spectrometry data. The antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method.

Synthesis and structure-affinity relationship of chlorinated pyrrolidinone-bearing benzenesulfonamides as human carbonic anhydrase inhibitors.

A novel set of pyrrolidinone-based chlorinated benzenesulfonamide derivatives were synthesized and investigated for their binding affinity and selectivity against recombinant human carbonic anhydrases I-XIV using fluorescent thermal shift, p-nitrophenyl acetate hydrolysis and stopped-flow enzymatic inhibition assays. The hydrazones 10-22 prepared from 1-(2-chloro-4-sulfamoylphenyl)-5-oxopyrrolidine-3-carboxylic acid exhibited low nanomolar affinity against cancer-related CA IX (K in the range of 5.0-37 nM).

Synthesis of 1-(5-Chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives and Their Antioxidant Activity.

A series of novel 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives containing chloro, hydroxyl, isopropyl, nitro, nitroso, and amino substituents at benzene ring and 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives bearing heterocyclic moieties were synthesized. Antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method and reducing power assay. A number of compounds were identified as potent antioxidants.

Pyrrolidinone-bearing methylated and halogenated benzenesulfonamides as inhibitors of carbonic anhydrases.

Two series of benzenesulfonamides bearing methyl groups at ortho/ortho or meta/ortho positions and a pyrrolidinone moiety at para position were synthesized and tested as inhibitors of the twelve catalytically active human carbonic anhydrase (CA) isoforms. Observed binding affinities were determined by fluorescent thermal shift assay and intrinsic binding affinities representing the binding of benzenesulfonamide anion to the Zn(II)-bound water form of CA were calculated. Introduction of dimethyl groups into benzenesulfonamide ring decreased the binding affinity to almost all CA isoforms, but gained in selectivity towards one CA isoform.