Synthesis, Antimicrobial, Anti-Virulence and Anticancer Evaluation of New 5(4H)-Oxazolone-Based Sulfonamides

Abstract

Since the synthesis of prontosil the first prodrug shares their chemical moiety, sulfonamides exhibit diverse modes of actions to serve as antimicrobials, diuretics, antidiabetics, and other clinical applications. This inspiring chemical nucleus has promoted several research groups to investigate the synthesis of new members exploring new clinical applications. In this study, a novel series of 5(4H)-oxazolone-based-sulfonamides (OBS) 9a-k were synthesized, and their antibacterial and antifungal activities were evaluated against a wide range of Gram-positive and -negative bacteria and fungi. Most of the tested compounds exhibited promising antibacterial activity against both Gram-positive and -negative bacteria particularly OBS 9b and 9f. Meanwhile, compound 9h showed the most potent antifungal activity. Moreover, the OBS 9a, 9b, and 9f that inhibited the bacterial growth at the lowest concentrations were subjected to further evaluation for their anti-virulence activities against Pseudomonas aeruginosa and Staphylococcus aureus. Interestingly, the three tested compounds reduced the biofilm formation and diminished the production of virulence factors in both P. aeruginosa and S. aureus. Bacteria use a signaling system, quorum sensing (QS), to regulate their virulence. In this context, in silico study has been conducted to assess the ability of OBS to compete with the QS receptors. The tested OBS showed marked ability to bind and hinder QS receptors, indicating that anti-virulence activities of OBS could be due to blocking QS, the system that controls the bacterial virulence. Furthermore, anticancer activity has been further performed for such derivatives. The OBS compounds showed variable anti-tumor activities, specifically 9a, 9b, 9f and 9k, against different cancer lines. Conclusively, the OBS compounds can serve as antimicrobials, anti-virulence and anti-tumor agents.

Sodium Citrate Alleviates Virulence in Pseudomonas aeruginosa

“…The virulent P. aeruginosa pyocyanin pigment was assayed in the presence or absence of sodium citrate, as previously shown [ 37 , 38 ]. Ten microliter aliquots of P. aeruginosa overnight cultures (adjusted to OD600 of 0.4) were mixed with 1 mL of LB broth provided with sodium citrate (4% or 5%).…”

Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap

“…A potent peptidyl inhibitor of aspartic proteases is bioconversion into an opensource antimalarial compound of P. falciparum prodrug activation and resistance esterase (PfPARE), MMV011438 is a good example (Istvan et al, 2017). Another representative prodrug, Prontosil, was reduced to sulfanilamide (SN) with antibacterial activity (Almalki et al, 2022). Another promising new class of drugs, proteolysis-targeting chimera (PROTAC), is also inseparable from the participation of metabolic enzymes (Békés et al, 2022).…”

Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens

“…QS controls bacterial virulence such as biofilm formation, motility, production of enzymes and other virulence factors [ 32 , 33 , 34 , 35 ]. Due to the key roles of QS, several studies screened the anti-QS activities of various chemical moieties [ 36 , 37 , 38 ], natural products [ 39 , 40 ], and approved safe drugs [ 41 , 42 , 43 , 44 ].…”