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Design, synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens. | LitMetric

AI Article Synopsis

Article Abstract

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria. Benzenediol compounds , , , , , and demonstrated broad spectrum antimicrobial actions, including resistant and multidrug-resistant species of dermatophytes (), spp. and the ESKAPE panel of bacteria. Minimum inhibitory concentrations of these compounds for fungi and bacterial strains ranged from 25 to 50 µg/ml and 8-128 µg/ml, respectively. The antifungal mechanism of action is related to the fungal cell wall of dermatophytes and membrane disruption to dermatophytes and yeasts, in the presence of compound . Specific structural changes, such as widespread thinning along the hyphae and yeast lysis, were observed by scanning electron microscopy. The effects of compound on cell viability are dose-dependent; however they did not cause genotoxicity and mutagenicity in human leukocyte cells nor haemolysis. Moreover, the compounds were identified as nonirritant by the Hen's egg test-chorioallantoic membrane (HET-CAM). The furan-1,4-benzenediol compound showed efficacy to combat infection using embryonated chicken eggs. Therefore, the compounds , and are promising as hits for the development of new antimicrobial drugs with reduced toxicity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921195PMC
http://dx.doi.org/10.1016/j.jsps.2019.09.003DOI Listing

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