Kyle Doherty , Keela Kessie , Harlei Martin , Jordan Loughlin , Oliwier Dulawa , Kaja Kasements , Trinidad Velasco-Torrijos
{"title":"Synthesis of aromatic glycoconjugates as anti-fungal agents against Candida spp. and assessment of their covalent crosslinking capabilities","authors":"Kyle Doherty , Keela Kessie , Harlei Martin , Jordan Loughlin , Oliwier Dulawa , Kaja Kasements , Trinidad Velasco-Torrijos","doi":"10.1016/j.bmc.2024.118020","DOIUrl":null,"url":null,"abstract":"<div><div>Covalent drugs are becoming increasingly attractive in drug discovery, as they can enhance potency and selectivity for their molecular targets. Covalent inhibitors have been investigated for several therapeutic applications, including anti-cancer and anti-infection agents. However, there are only a few examples of covalent inhibitors targeting fungal pathogens. We have previously reported aromatic glycoconjugates (AGCs) capable of inhibiting the adhesion of <em>Candida albicans</em> to buccal epithelial cells. In this work, we synthesize novel derivatives of the AGCs to which we have added reactive functional groups, such as acryloyl and vinyl sulfones, and investigated their antifungal efficacy against <em>Candida</em> spp<em>.</em> Although the compounds were ineffective at clinically relevant concentrations, we found that some of the galactose derivatives featuring reactive groups were amongst the most active, so their ability to crosslink nucleophilic side chains was assessed in model reactions.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"117 ","pages":"Article 118020"},"PeriodicalIF":3.3000,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089624004346","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Covalent drugs are becoming increasingly attractive in drug discovery, as they can enhance potency and selectivity for their molecular targets. Covalent inhibitors have been investigated for several therapeutic applications, including anti-cancer and anti-infection agents. However, there are only a few examples of covalent inhibitors targeting fungal pathogens. We have previously reported aromatic glycoconjugates (AGCs) capable of inhibiting the adhesion of Candida albicans to buccal epithelial cells. In this work, we synthesize novel derivatives of the AGCs to which we have added reactive functional groups, such as acryloyl and vinyl sulfones, and investigated their antifungal efficacy against Candida spp. Although the compounds were ineffective at clinically relevant concentrations, we found that some of the galactose derivatives featuring reactive groups were amongst the most active, so their ability to crosslink nucleophilic side chains was assessed in model reactions.
期刊介绍:
Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides.
The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.