Novel seleno-and thio-urea-containing dihydropyrrol-2-one analogues as antibacterial agents

Shekh Sabir; Tsz Tin Yu; Rajesh Kuppusamy; Basmah Almohaywi; George Iskander; Theerthankar Das; Mark D.P. Willcox; David Stclair Black; Naresh Kumar

doi:10.3390/antibiotics10030321

Novel seleno-and thio-urea-containing dihydropyrrol-2-one analogues as antibacterial agents

Shekh Sabir, Tsz Tin Yu, Rajesh Kuppusamy, Basmah Almohaywi, George Iskander, Theerthankar Das, Mark D.P. Willcox, David Stclair Black, Naresh Kumar

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.

Original language	English
Article number	321
Journal	Antibiotics
Volume	10
Issue number	3
DOIs	https://doi.org/10.3390/antibiotics10030321
Publication status	Published - Mar 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Antibacterial activity
Antibiotic resistance
Dihydropyrrol-2-one
Organoselenium compounds
Pseudomonas aeruginosa
Quorum-sensing inhibitors

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title = "Novel seleno-and thio-urea-containing dihydropyrrol-2-one analogues as antibacterial agents",

abstract = "The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.",

keywords = "Antibacterial activity, Antibiotic resistance, Dihydropyrrol-2-one, Organoselenium compounds, Pseudomonas aeruginosa, Quorum-sensing inhibitors",

author = "Shekh Sabir and Yu, {Tsz Tin} and Rajesh Kuppusamy and Basmah Almohaywi and George Iskander and Theerthankar Das and Willcox, {Mark D.P.} and Black, {David Stclair} and Naresh Kumar",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = mar,

doi = "10.3390/antibiotics10030321",

language = "English",

volume = "10",

journal = "Antibiotics",

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AU - Sabir, Shekh

AU - Yu, Tsz Tin

AU - Kuppusamy, Rajesh

AU - Almohaywi, Basmah

AU - Iskander, George

AU - Das, Theerthankar

AU - Willcox, Mark D.P.

AU - Black, David Stclair

AU - Kumar, Naresh

PY - 2021/3

Y1 - 2021/3

N2 - The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.

AB - The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.

KW - Antibacterial activity

KW - Antibiotic resistance

KW - Dihydropyrrol-2-one

KW - Organoselenium compounds

KW - Pseudomonas aeruginosa

KW - Quorum-sensing inhibitors

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DO - 10.3390/antibiotics10030321

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SN - 2079-6382

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JO - Antibiotics

JF - Antibiotics

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ER -

Novel seleno-and thio-urea-containing dihydropyrrol-2-one analogues as antibacterial agents

Abstract

Bibliographical note

Keywords

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