Sabir Shekh, Yu Tsz Tin, Kuppusamy Rajesh, Almohaywi Basmah, Iskander George, Das Theerthankar, Willcox Mark D P, Black David StClair, Kumar Naresh
School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
School of Optometry and Vision Science, The University of New South Wales, Sydney, NSW 2052, Australia.
Antibiotics (Basel). 2021 Mar 19;10(3):321. doi: 10.3390/antibiotics10030321.
The quorum sensing (QS) system in multi-drug-resistant bacteria such as 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 efficiently inhibited the 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 , and interestingly, only the selenium analogues showed antibacterial activity, with and being the most potent with a MIC of 15.6 µM.
诸如多药耐药细菌中的群体感应（QS）系统主要负责抗生素耐药性的产生，并且被认为是抗菌药物发现的一个有吸引力的靶点。在本研究中，我们合成了一系列新型含硒脲和硫脲的二氢吡咯 - 2 - 酮（DHP）类似物作为LasR拮抗剂。硒DHP衍生物表现出比相应的硫类似物显著更好的群体感应抑制（QSI）活性。最有效的类似物在125 µM时能有效抑制QS系统达81%，在31 µM时抑制率为53%。此外，对所有化合物针对革兰氏阳性细菌进行了最低抑菌浓度（MIC）筛选，有趣的是，只有硒类似物显示出抗菌活性，其中[具体化合物1]和[具体化合物2]最有效，MIC为15.6 µM。
