A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentadione (DPD) and related compounds as potential modulators of bacterial quorum sensing

Silvia Stotani, Viviana Gatta, Federico Medda, Mohan Padmanaban, Anna Karawajzyk, Päivi Sirpa Marjaana Tammela, Fabrizio Giordanetto, Dimitrios Tzalis, Simona Collina

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.

Original languageEnglish
Article number2545
JournalMolecules
Volume23
Issue number10
Number of pages22
ISSN1420-3049
DOIs
Publication statusPublished - 6 Oct 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • AI-2
  • AUTOINDUCER-2
  • COMMUNICATION
  • DERIVATIVES
  • DPD
  • DPD-related compounds
  • FUTURE PERSPECTIVES
  • SALMONELLA-TYPHIMURIUM
  • SIGNAL
  • SMALL-MOLECULE INHIBITORS
  • STEREOSELECTIVE-SYNTHESIS
  • TRIAZOLE
  • antibiotic resistance
  • quorum sensing
  • 116 Chemical sciences
  • 1182 Biochemistry, cell and molecular biology
  • 317 Pharmacy

Cite this

Stotani, Silvia ; Gatta, Viviana ; Medda, Federico ; Padmanaban, Mohan ; Karawajzyk, Anna ; Tammela, Päivi Sirpa Marjaana ; Giordanetto, Fabrizio ; Tzalis, Dimitrios ; Collina, Simona. / A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentadione (DPD) and related compounds as potential modulators of bacterial quorum sensing. In: Molecules. 2018 ; Vol. 23, No. 10.
@article{e671bd5423164176a2ea6ecead4e795d,
title = "A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentadione (DPD) and related compounds as potential modulators of bacterial quorum sensing",
abstract = "Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.",
keywords = "AI-2, AUTOINDUCER-2, COMMUNICATION, DERIVATIVES, DPD, DPD-related compounds, FUTURE PERSPECTIVES, SALMONELLA-TYPHIMURIUM, SIGNAL, SMALL-MOLECULE INHIBITORS, STEREOSELECTIVE-SYNTHESIS, TRIAZOLE, antibiotic resistance, quorum sensing, 116 Chemical sciences, 1182 Biochemistry, cell and molecular biology, 317 Pharmacy",
author = "Silvia Stotani and Viviana Gatta and Federico Medda and Mohan Padmanaban and Anna Karawajzyk and Tammela, {P{\"a}ivi Sirpa Marjaana} and Fabrizio Giordanetto and Dimitrios Tzalis and Simona Collina",
year = "2018",
month = "10",
day = "6",
doi = "10.3390/molecules23102545",
language = "English",
volume = "23",
journal = "Molecules",
issn = "1420-3049",
publisher = "MDPI",
number = "10",

}

A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentadione (DPD) and related compounds as potential modulators of bacterial quorum sensing. / Stotani, Silvia; Gatta, Viviana; Medda, Federico; Padmanaban, Mohan; Karawajzyk, Anna; Tammela, Päivi Sirpa Marjaana; Giordanetto, Fabrizio; Tzalis, Dimitrios; Collina, Simona.

In: Molecules, Vol. 23, No. 10, 2545, 06.10.2018.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - A versatile strategy for the synthesis of 4,5-dihydroxy-2,3-pentadione (DPD) and related compounds as potential modulators of bacterial quorum sensing

AU - Stotani, Silvia

AU - Gatta, Viviana

AU - Medda, Federico

AU - Padmanaban, Mohan

AU - Karawajzyk, Anna

AU - Tammela, Päivi Sirpa Marjaana

AU - Giordanetto, Fabrizio

AU - Tzalis, Dimitrios

AU - Collina, Simona

PY - 2018/10/6

Y1 - 2018/10/6

N2 - Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.

AB - Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to (S)-4,5-dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.

KW - AI-2

KW - AUTOINDUCER-2

KW - COMMUNICATION

KW - DERIVATIVES

KW - DPD

KW - DPD-related compounds

KW - FUTURE PERSPECTIVES

KW - SALMONELLA-TYPHIMURIUM

KW - SIGNAL

KW - SMALL-MOLECULE INHIBITORS

KW - STEREOSELECTIVE-SYNTHESIS

KW - TRIAZOLE

KW - antibiotic resistance

KW - quorum sensing

KW - 116 Chemical sciences

KW - 1182 Biochemistry, cell and molecular biology

KW - 317 Pharmacy

U2 - 10.3390/molecules23102545

DO - 10.3390/molecules23102545

M3 - Article

VL - 23

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 10

M1 - 2545

ER -