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

Antibiotics (Mar 2021)

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

Affiliations

Shekh Sabir: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Tsz Tin Yu: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Rajesh Kuppusamy: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Basmah Almohaywi: Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
George Iskander: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Theerthankar Das: Department of Infectious Diseases and Immunology, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia
Mark D. P. Willcox: School of Optometry and Vision Science, The University of New South Wales, Sydney, NSW 2052, Australia
David StClair Black: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Naresh Kumar: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia

DOI: https://doi.org/10.3390/antibiotics10030321
Journal volume & issue: Vol. 10, no. 3
p. 321

Abstract

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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.

Published in Antibiotics

ISSN: 2079-6382 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antibiotics

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