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Graphical abstract A series of quinolone-triazole conjugates synthesized as potential antiviral agents for SARS-CoV2. Some of the conjugates are more potent than the standards.

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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.

A series of new fluoroquinolone conjugates 8a-g and 9a-f were synthesized via benzotriazole-mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR-QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties. K E Y W O R D S antibacterial, dichloroacetic acid, DNA gyrase, fluoroquinolone, hybrid conjugates F I G U R E 1 Examples of different class of antibiotics 250 | SELIEM Et aL.to microwave irradiation (Discover mode; run time: 60 s; Power Max-cooling mode). N-(Boc-aminoacyl)benzotriazoles 10a-g (Panda, Hall, et al., 2014; Panda, Naumov, et al., 2014) Compounds 10a-g were synthesized by irradiating an equimolar amount of Boc-protected amino acid with 1-(methylsulfonyl)-1H-benzo[d] [1,2,3]triazole (BtSO 2 Me) in the presence of 2.0 eq. of triethylamine for 2 min run time and 60 min hold time at 70°C and 50 W irradiation power. Completion of the reaction was monitored by TLC. After completion of the reaction, the mixture was quenched with water. The product obtained was extracted with ethyl acetate and then washed with a saturated solution of sodium carbonate and water to afford compound 10a-g. | General procedure for the preparation of