The present study aims to investigate the antimicrobial as well as antivirulence potential and the principle mechanism of action of guaiacol against Pseudomonas aeruginosa.

https://academic.oup.com/jambio/article-pdf/133/4/2235/48732437/jambio2235.pdf

Guaiacol augments quorum quenching potential of ciprofloxacin against Pseudomonas aeruginosa

Exploration of seasonal fermentation differences and the possibility of flavor substances as regulatory factors in Daqu.

In this study, we report the chemical synthesis, computational analysis, and anti‐virulent studies of five Vanillin‐based hybrids employing phytochemicals. Vanillin (V) is known to have substantial anti‐quorum sensing activity against the gram‐negative pathogen Pseudomonas aeruginosa. Therefore, with the aim to further enhance the potency of Vanillin, it was chemically conjugated via a triazole (T) linker with five phytochemicals‐ Zingerone (Z), Eugenol (E), Guaiacol (G), Cinnamaldehyde (C), and Ferulic acid (F) to form the hybrids named as VTZ (1), VTE (2), VTG (3), VTC (4), and VTF (5), respectively. Molecular docking studies revealed the strong binding affinity of the designed hybrids with quorum‐sensing receptors (LasR, Rh1R, and PqsR). The synthesized hybrids were also evaluated for anti‐quorum sensing activities to examine the efficacy against P. aeruginosa bacterial strains PAO1. The hybrids VTE (2), VTG (3), and VTC (4) displayed improved anti‐quorum activity relative to Vanillin. Furthermore, the attenuation of virulence factors of P. aeruginosa (Las‐A protease, Las‐B elastase, pyocyanin pigmentation, and motility) in the presence of VTE (2), VTG (3), and VTC (4) further authenticated the anti‐virulent activity of the hybrids. The new design strategy of the phytochemical–phytochemical scaffolds and their biological evaluation provides a proof of concept for the simultaneous perturbation of well‐established anti‐virulent targets. This appears to be highly promising and effective strategy to ameliorate the enigma of antimicrobial resistance.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ddr.22011

Novel Vanillin‐based hybrids inhibit quorum sensing and silences phenotypical expressions in Pseudomonas aeruginosa

4-hydroxy 3-methoxy benzaldehyde (Vanillin) is an aromatic phenolic aldehyde with unique chemical properties and pharmacological impact. Because of its potent nature, it acts as a lead for drug discovery and development techniques. Heterocyclic compounds with vanillin moiety were efficacious and thrive against many emerging infectious diseases, which can also lead to develop numerous fused heterocyclic vanillin derivatives and various heterocyclic compounds such as pyrimidines, quinoxalines, imidazoles or thiazoles. Greener-mediated synthesis is a sustained chemical reaction used to synthesize hazardless vanillin derivatives with a high yield of product in desired time. Due to its several reasonable modifications with high bioactivity, vanillin moiety can be used to develop various potent derivatives like vanillin-based ferrocenyl chalcone derivatives, vanillin-hydrazone derivatives, Schiff base and Mannich base-based derivatives, pyrazoline vanillin-based derivatives, triazole-based vanillin derivatives and vanillin hybrids plays a crucial role in the coordination chemistry. These derivatives exhibited plenty of biological applications, which include anticancer, antioxidant, antibacterial, antitubercular, antimalarial, antiviral, anti-inflammatory, anti-Alzheimer and anti-diabetic effects. Hence, this review focuses on the significance of vanillin derivatives responsible for biological activity. 
Keywords: Vanillin; 4-hydroxy 3-methoxy benzaldehyde; Vanillin derivatives; Antimicrobial; Anticancer; Biological applications

Therapeutic aspects of biologically potent vanillin derivatives: A critical review

Quorum sensing-mediated microbial interactions: Mechanisms, applications, challenges and perspectives.

To address the issue of multidrug resistance in Pseudomonas aeruginosa, a novel catechol–zingerone conjugate (1) linked via a non-hydrolyzable 1,2,3-triazole linker was synthesized and subjected to biological evaluation based on the Trojan horse strategy. To enhance the efficacy, catechol, a xenosiderophore, utilized by P. aeruginosa for iron assimilation, and the dietary phytochemical zingerone, known for its anti-virulent activity against Pseudomonas aeruginosa, were exploited in the present study. Theoretical validation of conjugate (1) was conducted by in silico molecular docking analysis to determine the interaction with outer membrane transport receptor PirA and quorum sensing signal receptors. In addition, nine-fold binding affinity of Conjugate (1) toward PirA (5FP2) in comparison to its natural ligand catechol with D-score −1.13 Å authenticated the designed Trojan horse drug. Conjugate (1) showed stronger anti-virulent activity than zingerone; hence, it exhibited a promising anti-biofilm efficacy as assessed by crystal violet assay and visualized by FESEM toward P. aeruginosa. Encouraging results against P. aeruginosa in terms of quorum sensing regulated virulence factors, motility phenotypes, and biofilm formation with no cell cytotoxicity and could help open hitherto unexplored possibilities of establishing Trojan horse drugs as a successful approach against multidrug resistance in P. aeruginosa.

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Design, Synthesis, and Quorum Quenching Potential of Novel Catechol–Zingerone Conjugate to Find an Elixir to Tackle Pseudomonas aeruginosa Through the Trojan Horse Strategy

Aim: To study the influence of plant volatiles, bioactives and synthetic antibiotics on the attenuation of the quorum sensing (QS)-regulated virulence factors of Pseudomonas aeruginosa. Materials & methods: QS inhibition; the QS-regulated virulence factors pyocyanin, hemolysin, elastase, protease, alginate and pyochelin; and motility phenotypes were performed at sub-MIC to check the attenuation effect of 24 agents on the virulence of P. aeruginosa. Results: Eighteen out of 24 assayed compounds exhibited anti-QS activity and reduced the production of all virulence factors. Cinnamaldehyde, zingerone and lavender oil exhibited a significant reduction in motility phenotypes. Conclusion: Natural phytomolecules as a whole or their bioactives could be used to develop antivirulence drugs after in vivo evaluation.

Natural bioactives versus synthetic antibiotics for the attenuation of quorum sensing-regulated virulence factors of Pseudomonas aeruginosa.

Synthesis of bis(indolyl)methane/dihydropyrimidinone based bis-amide-triazole hybrid compounds has been achieved via one-pot six/seven-component sequential Ugi-Click reaction. Two molecular libraries of anti-bacterial compounds containing significant pharmacophoric nuclei were synthesized in good yield and purity using green solvent, mild reaction conditions with atom economy by structural modifications in three independent starting materials. 

Synthesis of Bis(indolyl)methane/Dihydropyrimidinone Tethered Bis‐Amidic Triazole Hybrid Compounds via One‐Pot Sequential Six/Seven Component Ugi‐Click Reaction

Surabhi Mangal

Papers

Guaiacol augments quorum quenching potential of ciprofloxacin against Pseudomonas aeruginosa

Novel Vanillin‐based hybrids inhibit quorum sensing and silences phenotypical expressions in Pseudomonas aeruginosa

Design, Synthesis, and Quorum Quenching Potential of Novel Catechol–Zingerone Conjugate to Find an Elixir to Tackle Pseudomonas aeruginosa Through the Trojan Horse Strategy

Natural bioactives versus synthetic antibiotics for the attenuation of quorum sensing-regulated virulence factors of Pseudomonas aeruginosa.

Synthesis of Bis(indolyl)methane/Dihydropyrimidinone Tethered Bis‐Amidic Triazole Hybrid Compounds via One‐Pot Sequential Six/Seven Component Ugi‐Click Reaction