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

Abstract

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 2 and 4–22 were subjected to the in vitro anticancer and antimicrobial activity determination. The compounds 18–22 exerted the most potent anticancer activity against A549 cells. Furthermore, compound 21 bearing 5-nitrothiophene substituents demonstrated promising and selective antimicrobial activity against multidrug-resistant Staphylococcus aureus strains, including linezolid and tedizolid-resistant S. aureus. These results demonstrate that 5-oxopyrolidine derivatives are attractive scaffolds for the further development of anticancer and antimicrobial compounds targeting multidrug-resistant Gram-positive pathogens.

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

“…Cytotoxicity assay. The in vitro inhibitory effects of the compounds were assessed using the MTT assay, as described in previous studies [24,25]. The A549 or THP-1 derived macrophages were seeded into 96-well plates at a concentration of 1 × 10 4 cells per well.…”

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

“…Therefore, the development of novel antimicrobial candidates, targeting multidrug-resistant Gram-positive pathogens and drug-resistant fungi, is critically needed. Our previous studies [31,32] on the development of novel compounds targeting multidrug-resistant pathogens have been reasonably successful in finding effective antimicrobial agents and showed higher bactericidal properties than ampicillin; therefore, we have continued the studies in this field. As the results demonstrate that 5-oxopyrolidine derivatives are attractive cores for the further development of potential candidates targeting multidrug-resistant Gram-positive pathogens and drug-resistant fungi with genetically defined resistance mechanisms, herein, we report the synthesis and bioevaluation of compounds having N-(2-hydroxyphenyl)and N-(3,5-dichloro-2-hydroxyphenyl)-5-oxopyrrolidin-3-yl cores, as well their decyclization products, γ-amino acid derivatives.…”

An investigation of the biological applications of sulphonated succinimides: in vivo toxicity to zebrafish larvae as well as antioxidant and antimicrobial potential

“…Antibacterial studies of succinimide and sulphonyl moieties have also been reported. Some of the studies include 5-oxopyrrolidine derivatives against Staphylococcus aureus (Gram-positive bacterium directed activity), 30 pyrrolidine-2,5dione against Escherichia coli and Streptococcus pneumoniae, 31 N-aryl succinimide against S. aureus ATCC 25923 (Gram-positive bacterium) and K. pneumoniae 22, Salmonella 68R (Gramnegative bacterium), 32 N-sulfonamide 2-pyridones against Klebsiella pneumonia, Pseudomonas aeruginosa (Gram-negative bacterium) and Streptococcus mutans, Staphylococcus aureus (Gram-positive bacterium), 33 folic acid-sulfonamide conjugates against Gram-negative (P. aeruginosa and E. coli) and Grampositive (S. aureus and P. mirabilis) bacteria. 34 Based on the above reports and the biological importance of the succinimide moiety and sulphonyl scaffolds, significant interest has arisen in designing hybrid compounds of succinimide with sulphonyls to explore their biological activities.…”