Design, synthesis, biological evaluation and toxicity studies of N,N-disubstituted biguanides as quorum sensing inhibitors

Singh, Shaminder; Wanjari, Pravin J.; Bhatia, Sonam; Sonwane, Vijay C.; Chakraborti, Asit K.; Bharatam, Prasad V.

doi:10.1007/s00044-014-1255-y

Cited by 20 publications

(18 citation statements)

References 60 publications

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“…As mentioned earlier, both of the assayed traits are under the control of QS. 20 , 21 Interestingly, we found that albendazole has anti-QS activities in sub-MICs in a dose-dependent manner. Therefore, it can inhibit violacein production in C. violaceum .…”

Section: Introductionmentioning

confidence: 77%

“…This finding is also noticed by us in the previous study where N,N -disubstituted biguanides with aryl groups have shown a significant correlation between π stacking ability and observed biological activity. 21 …”

Section: Resultsmentioning

confidence: 99%

“… 19 We are working in the area of QS and screening several secondary metabolites produced by microorganisms subsequent to their QSI activity. 20 , 21 We have standardized various bioassays by testing several known inhibitors of QS against violacein pigment production in Chromobacterium violaceum and also green fluorescence protein production in P. aeruginosa lasB-gfp strain. As mentioned earlier, both of the assayed traits are under the control of QS.…”

Section: Introductionmentioning

confidence: 99%

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In silico identification of albendazole as a quorum sensing inhibitor and its in vitro verification using CviR and LasB receptors based assay systems

Singh¹,

Bhatia²

2018

Bioimpacts

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Introduction:Quorum sensing inhibition (QSI) is one of the vital tools to overcome emerging virulence of pathogenic bacteria which aims at curbing bacterial resistance. Targeting QS (quorum sensing) as chemotherapy is less likely to generate resistance among pathogens as it targets only the adaptation and not the survival mechanism of the pathogen. Several QS inhibitors were developed in the recent past but none of them managed to have clinical application due to known toxic effects for human consumption. A rapid development of QS inhibitor drugs could be achieved by verification of the QSI activity of drugs which are already in clinical use with known pharmacology. Recently, a known FDA approved clinical drug niclosamide belonging to an anthelmintic class is found to exhibit QSI activity. Methods: We have focused our study on Albendazole, another FDA approved clinical drug belonging to the same class for its potential to act as QSI. The structure-based molecular docking is used for finding putative interactions made by this drug with the CviR and LasB receptor protein of Chromobacterium violaceum and Pseudomonas aeruginosa , respectively. Further, the in vitro activity of this drug has been evaluated by employing CviR and LasB receptor-based bioassay. The efficacy of this drug alone and in combination with antibiotic Tobramycin to inhibit P. aeruginosa based biofilms was also analyzed by developing the biofilms on chambered glass slides and performing anti-biofilm assay. Results: Further, this drug found to inhibit purple pigment violacein production in C. violaceum , which is under the control of C6-AHL-CviR mediated QS in this human pathogen. The in vivo bioassays results suggested that albendazole has great potential to act as a QS inhibitor as found inhibiting violacein production in C. violaceum and biofilm formation in P. aeruginosa , respectively. Conclusion: It is that structure-based molecular docking guided bioassay evaluation is an efficient tool for finding the new therapeutic use of old drugs which could have more chances to come easily in clinical application for their newly identified therapeutic uses.

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Section: Introductionmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In silico identification of albendazole as a quorum sensing inhibitor and its in vitro verification using CviR and LasB receptors based assay systems

Singh¹,

Bhatia²

2018

Bioimpacts

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“…The reaction was completed within 15 minutes with a clean conversion and good yields (86-89%). Similar conditions were used by Singh et al to afford N 1 ,N 1 -dialkylbiguanides (Scheme 7B) [23]. While the authors observed a remarkable rate acceleration of several orders of magnitude over conventional heating, little was understood about the role of microwaves on this specific conversion, i.e., thermal or non-thermal effects.…”

Section: Methodsmentioning

confidence: 78%

Synthetic accesses to biguanide compounds

Grytsai

Ronco

Benhida

2021

Beilstein J. Org. Chem.

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Biguanide is a unique chemical function, which has attracted much attention a century ago and is showing resurgent interest in recent years after a long period of dormancy. This class of compounds has found broad applications such as reaction catalysts, organic strong bases, ligands for metal complexation, or versatile starting materials in organic synthesis for the preparation of nitrogen-containing heterocycles. Moreover, biguanides demonstrate a wide range of biological activities and some representatives are worldwide known such as metformin, the first-line treatment against type II diabetes, or chlorhexidine, the gold standard disinfectant and antiseptic. Although scarcely represented, the number of “success stories” with biguanide-containing compounds highlights their value and their unexploited potential as future drugs in various therapeutic fields or as efficient metal ligands. This review provides an extensive and critical overview of the synthetic accesses to biguanide compounds, as well as their comparative advantages and limitations. It also underlines the need of developing new synthetic methodologies to reach a wider variety of biguanides and to overcome the underrepresentation of these compounds.

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“…Compound 10 l was considered as a novel quorum sensing inhibitor. Moreover, a series of N , N ‐disubstituted biguanides as quorum sensing inhibitors have been synthesized . Among them, three N , N ‐disubstituted biguanides analogues could inhibit 20%‐50% violacein production of C. violaceum ATCC 12472 at 0.2 mM.…”

Section: Quorum Sensing Inhibitory Activitymentioning

confidence: 99%

Synthesis and In Vitro Antibacterial Activity of Novel Naphthyridinone Derivatives

Sun

Chen

et al. 2019

ChemistrySelect

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Naphthyridinone has been reported exhibiting strong antibacterial activity. Now, this study describes a series of novel hydrochloride salts of 5,6,7,8‐tetrahydro‐1,6‐naphthyridin‐2‐(1H)‐one derivatives (10 a–10 l) as potential antibacterial agents and corresponding synthetic routes. The majority of analogues exhibit antibacterial activity against Gram‐negative bacteria (E. coli) and Gram‐positive bacteria (S. aureus). Several of them (10 a, 10 b, 10 h and 10 i) showed strongly antibacterial activity towards E. coli. Compound 10 l is also the first reported compound to exhibit quorum sensing inhibitory activity against C. violaceum ATCC 12472. The presence of quorum sensing inhibitory compound indicates its potential use in the treatment of bacterial infections.

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Design, synthesis, biological evaluation and toxicity studies of N,N-disubstituted biguanides as quorum sensing inhibitors

Cited by 20 publications

References 60 publications

In silico identification of albendazole as a quorum sensing inhibitor and its in vitro verification using CviR and LasB receptors based assay systems

In silico identification of albendazole as a quorum sensing inhibitor and its in vitro verification using CviR and LasB receptors based assay systems

Synthetic accesses to biguanide compounds

Synthesis and In Vitro Antibacterial Activity of Novel Naphthyridinone Derivatives

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