Benzotriazole-Mediated Synthesis and Antibacterial Activity of Novel N-Acylcephalexins

Agha, Khalid A.; Abo‐Dya, Nader E.; Ibrahim, Tarek S.; Abdel‐Aal, Eatedal H.; Hegazy, Wael A. H.

doi:10.3390/scipharm84030484

Cited by 25 publications

(13 citation statements)

References 21 publications

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“…The decreased numbers of newly discovered efficient antibiotics cannot resolve this issue and bacterial resistance development is augmented to be one of the major public health problems [ 52 , 53 ]. In this context, several approaches have been proposed; targeting bacterial resistance is a promising one [ 16 , 31 , 54 , 55 ]. This approach confers anti-virulence agents that can be used in addition to antibiotics in particular in aggressive resistant bacterial infections [ 2 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities

et al. 2022

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The targeting of bacterial virulence is proposed as a promising approach to overcoming the bacterial resistance development to antibiotics. Salmonella enterica is one of the most important gut pathogens that cause a wide diversity of local and systemic illnesses. The Salmonella virulence is controlled by interplayed systems namely Quorum sensing (QS) and type three secretion system (T3SS). Furthermore, the Salmonella spy on the host cell via sensing the adrenergic hormones enhancing its virulence. The current study explores the possible anti-virulence activities of β-adrenoreceptor blocker atenolol against S. enterica serovar Typhimurium in vitro, in silico, and in vivo. The present findings revealed a significant atenolol ability to diminish the S. Typhimurium biofilm formation, invasion into HeLa cells, and intracellular replication inside macrophages. Atenolol significantly downregulated the encoding genes of the T3SS-type II, QS receptor Lux analogs sdiA, and norepinephrine membranal sensors qseC and qseE. Moreover, atenolol significantly protected mice against S. Typhimurium. For testing the possible mechanisms for atenolol anti-virulence activities, an in silico molecular docking study was conducted to assess the atenolol binding ability to QS receptor SdiA and norepinephrine membranal sensors QseC. Atenolol showed the ability to compete on the S. Typhimurium targets. In conclusion, atenolol is a promising anti-virulence candidate to alleviate the S. Typhimurium pathogenesis by targeting its QS and T3SS systems besides diminishing the eavesdropping on the host cells.

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Section: Discussionmentioning

confidence: 99%

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities

et al. 2022

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“…Among the proven efficient approaches, the attenuation of bacterial virulence is considered a promising one [ 57 , 58 ]. Several studies have been conducted to mitigate bacterial virulence by a wide diversity of chemical and natural compounds [ 30 , 31 , 32 , 34 , 59 ]. Particularly, the anti-virulence activities of several approved safe drugs were investigated prior to their repurposing to serve as adjuvants to antibiotics [ 31 , 32 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against Salmonella enterica

et al. 2022

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Salmonella enterica is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. Salmonella enterica utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, S. enterica could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of S. enterica serovar Typhimurium. The prazosin effect on biofilm formation and the expression of sdiA, qseC, qseE, and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against S. typhimurium. The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities.

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“…The MICs of the synthesized compound were determined by agar dilution method according to the Clinical Laboratory and Standards Institute Guidelines (CLSI, 2015) [55,64]. Briefly, the tested strains were incubated overnight in tryptic soy broth (TSB) (Oxoid, United Kingdom) and then diluted in Muller-Hinton (MH) broth (Oxoid, United Kingdom) to turbidity approximating to the equivalent of 0.5 McFarland standard [65]. The suspensions were further diluted with sterile saline (1:10) and standardized inoculums (approximately 10 4 CFU per spot) were spotted on the surfaces of MH agar (Oxoid, United Kingdom) plates containing different concentrations of tested compounds and a control plate.…”

Section: General Procedures For the Synthesis Of 2-((4-methylphenyl)sulfonamido)benzoic Acidmentioning

confidence: 99%

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

et al. 2022

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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.

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Benzotriazole-Mediated Synthesis and Antibacterial Activity of Novel N-Acylcephalexins

Cited by 25 publications

References 21 publications

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities

Silencing of Salmonella typhimurium Pathogenesis: Atenolol Acquires Efficient Anti-Virulence Activities

Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against Salmonella enterica

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

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