Synthesis and Study of Antibiofilm and Antivirulence Properties of Flavonol Analogues Generated by Palladium Catalyzed Ligand Free Suzuki-Miyaura Coupling Against PAO1

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Apr 18

PMID 38633488

Authors

Anjitha Theres Benny

Masthan Thamim

Prakhar Srivastava

Sindoora Suresh

Krishnan Thirumoorthy

Loganathan Rangasamy

Karthikeyan S

Nalini Easwaran

Ethiraj Kannatt Radhakrishnan

Affiliations

Soon will be listed here.

Abstract

The Suzuki-Miyaura coupling is one of the ubiquitous method for the carbon-carbon bond-forming reactions in organic chemistry. Its popularity is due to its ability to undergo extensive coupling reactions to generate a broad range of biaryl motifs in a straightforward manner displaying a high level of functional group tolerance. A convenient and efficient synthetic route to arylate different substituted flavonols through the Suzuki-Miyaura cross-coupling reaction has been explained in this study. The arylated products were acquired by the coupling of a variety of aryl boronic acids with flavonols under Pd(OAc) catalyzed reaction conditions in a ligand-free reaction strategy. Subsequently, the antibiofilm and antivirulence properties of the arylated flavonols against PAO1 were studied thoroughly. The best ligands for quorum sensing proteins LasR, RhlR, and PqsR were identified using molecular docking study. These best fitting ligands were then studied for their impact on gene expression level of by RT-PCR towards quorum sensing genes , , and . The downregulation in the gene expression with the effect of synthesized flavonols endorse the antibiofilm efficiency of the compounds.

References

Di Martino P . Extracellular polymeric substances, a key element in understanding biofilm phenotype. AIMS Microbiol. 2019; 4(2):274-288. PMC: 6604936. DOI: 10.3934/microbiol.2018.2.274. View

Johansson Seechurn C, Kitching M, Colacot T, Snieckus V . Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 Nobel Prize. Angew Chem Int Ed Engl. 2012; 51(21):5062-85. DOI: 10.1002/anie.201107017. View

Silver L, Bostian K . Screening of natural products for antimicrobial agents. Eur J Clin Microbiol Infect Dis. 1990; 9(7):455-61. DOI: 10.1007/BF01964283. View

Lu L, Hu W, Tian Z, Yuan D, Yi G, Zhou Y . Developing natural products as potential anti-biofilm agents. Chin Med. 2019; 14:11. PMC: 6425673. DOI: 10.1186/s13020-019-0232-2. View

James C, Coelho A, Gevaert M, Forgione P, Snieckus V . Combined directed ortho and remote metalation-Suzuki cross-coupling strategies. Efficient synthesis of heteroaryl-fused benzopyranones from biaryl O-carbamates. J Org Chem. 2009; 74(11):4094-103. DOI: 10.1021/jo900146d. View

Mouffouk C, Mouffouk S, Mouffouk S, Hambaba L, Haba H . Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CL and PL), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). Eur J Pharmacol. 2020; 891:173759. PMC: 7691142. DOI: 10.1016/j.ejphar.2020.173759. View

Qin C, Chen X, Hughes R, Williams S, Woodman O . Understanding the cardioprotective effects of flavonols: discovery of relaxant flavonols without antioxidant activity. J Med Chem. 2008; 51(6):1874-84. DOI: 10.1021/jm070352h. View

Luo J, Dong B, Wang K, Cai S, Liu T, Cheng X . Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model. PLoS One. 2017; 12(4):e0176883. PMC: 5409170. DOI: 10.1371/journal.pone.0176883. View

Gao L, Tang Z, Li T, Wang J . Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice. Microb Pathog. 2023; 182:106165. DOI: 10.1016/j.micpath.2023.106165. View

10.

Lindsay S, Oates A, Bourdillon K . The detrimental impact of extracellular bacterial proteases on wound healing. Int Wound J. 2017; 14(6):1237-1247. PMC: 7949928. DOI: 10.1111/iwj.12790. View

11.

Lennox A, Lloyd-Jones G . Selection of boron reagents for Suzuki-Miyaura coupling. Chem Soc Rev. 2013; 43(1):412-43. DOI: 10.1039/c3cs60197h. View

12.

Diggle S, Whiteley M . Microbe Profile: : opportunistic pathogen and lab rat. Microbiology (Reading). 2019; 166(1):30-33. PMC: 7273324. DOI: 10.1099/mic.0.000860. View

13.

Chirumbolo S . The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets. 2010; 9(4):263-85. DOI: 10.2174/187152810793358741. View

14.

Maisetta G, Piras A, Motta V, Braccini S, Mazzantini D, Chiellini F . Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against . Microorganisms. 2021; 9(5). PMC: 8145479. DOI: 10.3390/microorganisms9050912. View

15.

Krzyzek P, Migdal P, Paluch E, Karwanska M, Wieliczko A, Gosciniak G . Myricetin as an Antivirulence Compound Interfering with a Morphological Transformation into Coccoid Forms and Potentiating Activity of Antibiotics against . Int J Mol Sci. 2021; 22(5). PMC: 7962197. DOI: 10.3390/ijms22052695. View

16.

Tuon F, Dantas L, Suss P, Ribeiro V . Pathogenesis of the Biofilm: A Review. Pathogens. 2022; 11(3). PMC: 8950561. DOI: 10.3390/pathogens11030300. View

17.

Hall S, McDermott C, Anoopkumar-Dukie S, McFarland A, Forbes A, Perkins A . Cellular Effects of Pyocyanin, a Secreted Virulence Factor of Pseudomonas aeruginosa. Toxins (Basel). 2016; 8(8). PMC: 4999852. DOI: 10.3390/toxins8080236. View

18.

Rendekova K, Fialova S, Janosova L, Mucaji P, Slobodnikova L . The Activity of Cotinus coggygria Scop. Leaves on Staphylococcus aureus Strains in Planktonic and Biofilm Growth Forms. Molecules. 2016; 21(1):E50. PMC: 6273237. DOI: 10.3390/molecules21010050. View

19.

Moon Y, Wang X, Morris M . Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2005; 20(2):187-210. DOI: 10.1016/j.tiv.2005.06.048. View

20.

Rajkumari J, Magdalane C, Siddhardha B, Madhavan J, Ramalingam G, Al-Dhabi N . Synthesis of titanium oxide nanoparticles using Aloe barbadensis mill and evaluation of its antibiofilm potential against Pseudomonas aeruginosa PAO1. J Photochem Photobiol B. 2019; 201:111667. DOI: 10.1016/j.jphotobiol.2019.111667. View