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Special Issue "Design and Synthesis of Quorum-Sensing Inhibitors"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Synthesis".

Deadline for manuscript submissions: closed (15 October 2017)

Special Issue Editor

Guest Editor
Prof. Dr. Naresh Kumar

School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Website | E-Mail
Interests: quorum sensing inhibitors; antimicrobial biomaterials; antimicrobial peptides and mimics; RNAP-σ factor inhibitors; dual-action antimicrobials

Special Issue Information

Dear Colleagues,

With the long-term overuse and misuse of antibiotics, the problem of antibiotic-resistance is now reaching a critical stage. Antibiotics are no longer the magic bullets they were once thought to be and therefore there is an urgent need for development of alternative therapeutic strategies to combat infections without inducing drug resistance. Quorum-sensing (QS) inhibition presents a promising alternative strategy, since it attenuates bacterial virulence by disrupting the signaling pathway between bacteria without inducing stress.

Several strategies to combat this problem are discussed:

i)     Isolation of natural products with quorum sensing (QS) inhibitory activities and developing their synthetic analogues;
ii)    Synthesis of new classes of QSI with anti-virulence and anti-biofilm properties;
iii)   Rational design of QSIs;
iv)   Structure-activity relationship studies of QSIs;
v)    Applications and targeted delivery of QSIs;
vi)   Dual-action and hybrid QSIs;
vii)  Synergistic activities of QSIs.

Molecules will publish a Special Issue focusing on the “Design and Synthesis of Quorum-Sensing Inhibitors”, as well as novel molecular targets with reduced capacity to develop antibiotic resistance. It is my pleasure to invite submissions of high quality research-based papers related to the topics mentioned above.

Prof. Naresh Kumar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Discovery of new classes of quorum sensing inhibitors
  • Synthesis of quorum sensing inhibitors with antimicrobial activity
  • Rational design of quorum sensing inhibitors
  • Development of methods for the targeted delivery of quorum sensing inhibitors

Published Papers (3 papers)

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Research

Open AccessArticle Modification and Assembly of a Versatile Lactonase for Bacterial Quorum Quenching
Molecules 2018, 23(2), 341; doi:10.3390/molecules23020341
Received: 14 December 2017 / Revised: 23 January 2018 / Accepted: 23 January 2018 / Published: 6 February 2018
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Abstract
This work sets out to provide a self-assembled biopolymer capsule activated with a multi-functional enzyme for localized delivery. This enzyme, SsoPox, which is a lactonase and phosphotriesterase, provides a means of interrupting bacterial communication pathways that have been shown to mediate pathogenicity.
[...] Read more.
This work sets out to provide a self-assembled biopolymer capsule activated with a multi-functional enzyme for localized delivery. This enzyme, SsoPox, which is a lactonase and phosphotriesterase, provides a means of interrupting bacterial communication pathways that have been shown to mediate pathogenicity. Here we demonstrate the capability to express, purify and attach SsoPox to the natural biopolymer chitosan, preserving its activity to “neutralize” long-chain autoinducer-1 (AI-1) communication molecules. Attachment is shown via non-specific binding and by engineering tyrosine and glutamine affinity ‘tags’ at the C-terminus for covalent linkage. Subsequent degradation of AI-1, in this case N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL), serves to “quench” bacterial quorum sensing (QS), silencing intraspecies communication. By attaching enzymes to pH-responsive chitosan that, in turn, can be assembled into various forms, we demonstrate device-based flexibility for enzyme delivery. Specifically, we have assembled quorum-quenching capsules consisting of an alginate inner core and an enzyme “decorated” chitosan shell that are shown to preclude bacterial QS crosstalk, minimizing QS mediated behaviors. Full article
(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)
Figures

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Open AccessFeature PaperArticle In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa
Molecules 2018, 23(2), 257; doi:10.3390/molecules23020257
Received: 22 December 2017 / Revised: 20 January 2018 / Accepted: 20 January 2018 / Published: 28 January 2018
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Abstract
Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of
[...] Read more.
Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P. aeruginosa mCTX::PpqsA-lux chromosomal promoter fusion, to identify a series of new PqsR antagonists. The hit compounds inhibited pyocyanin and alkylquinolone signal molecule production in P. aeruginosa PAO1-L and PA14 strains. The inhibitor Ia, which showed the highest activity in PA14, reduced biofilm formation in PAO1-L and PA14, increasing their sensitivity to tobramycin. Furthermore, the hepatic and plasma stabilities for these compounds were determined in both rat and human in vitro microsomal assays, to gain a further understanding of their therapeutic potential. This work has uncovered a new class of P. aeruginosa PqsR antagonists with potential for hit to lead optimisation in the search for quorum sensing inhibitors for future anti-infective drug discovery programs. Full article
(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)
Figures

Open AccessFeature PaperArticle 2-Substituted Aniline as a Simple Scaffold for LuxR-Regulated QS Modulation
Molecules 2017, 22(12), 2090; doi:10.3390/molecules22122090
Received: 29 September 2017 / Revised: 17 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
PDF Full-text (2950 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ability of the 2-substituted aniline motif to serve as a scaffold for designing potential LuxR-regulated quorum sensing (QS) modulators has been investigated, using docking experiments and biological evaluation of a series of 15 specially synthesized compounds. Aniline, 2-acetyl-aniline and 2-nitroaniline were considered,
[...] Read more.
The ability of the 2-substituted aniline motif to serve as a scaffold for designing potential LuxR-regulated quorum sensing (QS) modulators has been investigated, using docking experiments and biological evaluation of a series of 15 specially synthesized compounds. Aniline, 2-acetyl-aniline and 2-nitroaniline were considered, as well as their N-acylated derivatives. Docking experiments showed that the 2-substituted aniline motif fits within the LuxR binding site at the place of the lactone moiety of AHL, and the biological evaluation revealed QS antagonisitic activity for several compounds, validating the hypothesis that this scaffold acts on QS. Structure activity relationships are discussed regarding interactions with the key residues of the LuxR binding site, showing significant variations in the H-bonding pattern. Full article
(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)
Figures

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