The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus 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 S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC50 = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC50 = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC50 = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286.

The p-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 Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Salmonella enteritidis, Escherichia coli, and Pseudomonas aeruginosa by using MIC and MBC assays. This study showed a good bactericidal activity of γ-amino acid and benzimidazoles derivatives. The antimicrobial activity of the most promising compounds was higher than ampicillin. Furthermore, two benzimidazoles demonstrated good antimicrobial activity against L. monocytogenes (MIC 15.62 µg/mL) that was four times more potent than ampicillin (MIC 65 µg/mL). Further studies are needed to better understand the mechanism of the antimicrobial activity as well as to generate antimicrobial compounds based on the 1-phenyl-5-oxopyrrolidine scaffold.

A series of substituted thiazoles bearing different functional groups, such as carboxyethylamino, carboxyl, chloromethyl, (phenylamino)methyl, ethoxyoxoethyl, methoxyoxoethylidene, ethoxycarbonyl, (methoxy or hydrazinyl)oxopropyl, carbohydrazinyl, formyl, and ((phenyl, carbamothioyl or isonicotinoyl)hydrazono)methyl, incorporated into their structure were synthesized. The synthesized compounds were tested for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Mycobacterium luteum bacteria strains, and Candida tenuis and Aspergillus niger fungi. Compounds exhibiting exclusive antifungal activity against Aspergillus niger (MIC 0.9, 1.9 μg/mL) and Candida tenuis (MIC 7.8 μg/mL) have been identified among the novel thiazole derivatives.

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. The obtained results were compared with those of the standard antiviral, antioxidant, antibacterial and anticancer agents. The compound bearing 4-cianophenyl substituent in the thiazole ring demonstrated the highest cytotoxic properties by decreasing the A549 viability to 87.2%. The compound bearing 4-trifluoromethylphenyl substituent in the thiazole ring showed significant antiviral activity against the PR8 influenza A strain, which was comparable to the oseltamivir and amantadine. Novel compounds with 4-chlorophenyl, 4-trifluoromethylphenyl, phenyl, 4-fluorophenyl, and 4-cianophenyl substituents in the thiazole ring demonstrated antioxidant activity by DPPH, reducing power, FRAP methods, and antibacterial activity against Escherichia coli and Bacillus subtilis bacteria. These data demonstrate that substituted aminothiazole derivatives are promising scaffolds for further optimization and development of new compounds with potential influenza A-targeted antiviral activity. Study results could demonstrate that structure optimization of novel aminothiazole compounds may be useful in the prevention of reactive oxygen species and developing new specifically targeted antioxidant and antibacterial agents.

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. The biological evaluation of compounds 9–16 showed promising structure-dependent anticancer activity on A549 cells in 2D and 3D models. Compounds were able to significantly (p < 0.05) reduce the A549 viability after 24 h of treatment in comparison to treated control. Compounds 9 and 16 bearing phenylamino and 4-hydroxyphenylamino substituents demonstrated the most promising anticancer activity and were able to induce mitochondrial damage and ROS formation. Furthermore, most promising compounds showed significantly lower cytotoxicity to non-cancerous Vero cells. The in silico ADMET properties revealed promising drug-like properties of compounds 9 and 16. Both compounds demonstrated favorable predicted GI absorption values, while only 16 was predicted to be permeable through the blood–brain barrier. Molecular modeling studies identified that compound 16 is able to interact with COX-2 in arachidonic acid site. Further studies are needed to better understand the safety and in vivo efficacy of compounds 9 and 16.

A series of novel 1,2‐bissubstituted disulfanes bearing beta‐amino acid, dihydropyrimidine‐2,4‐(1H,3H)‐dione, hydrazide, hydrazone and azole moieties were synthesized. The antibacterial activity was evaluated by determining minimum inhibition (by broth microdilution) and minimum bactericidal (by growth on agar) concentrations. The assessment revealed that MIC values for L. monocytogenes varied between 3.9 and 62.5 μg/mL as well as for S. aureus ranged between 7.8 and 250 μg/mL, with the exception of one compound with much weaker MIC of 500 μg/mL. The MBC values for L. monocytogenes have been found to be of 7.8–250 μg/mL, while S. aureus demonstrated the higher resistance and MBCs varied in the range of 7.8–500 μg/mL. The determined MBC/MIC ratios showed that eleven compounds were classified bactericidal agents for all tested bacteria.

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. The in silico ADME characterization revealed that compounds 1–9 meet at least 2 Lipinski drug-like properties while cytotoxicity studies demonstrated low cytotoxicity to Vero cells. Further in vitro antimicrobial activity characterization showed the selective and potent bactericidal activity of 2a–c against Gram-positive pathogens (MIC 1–64 µg/mL) with profound activity against S. aureus (MIC 1–2 µg/mL) harboring genetically defined resistance mechanisms. Furthermore, the compounds 2a–c exhibited antifungal activity against azole resistant A. fumigatus, while only 2b and 5a showed antifungal activity against multidrug resistant yeasts including Candida auris. Collectively, these results demonstrate that thiazole derivatives 2a–c and 5a could be further explored as a promising scaffold for future development of antifungal and antibacterial agents targeting highly resistant pathogenic microorganisms.

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