{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:23:57Z","timestamp":1789079037836,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Purdue University","award":["R01AI130186"],"award-info":[{"award-number":["R01AI130186"]}]},{"DOI":"10.13039\/100000002","name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI130186"],"award-info":[{"award-number":["R01AI130186"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus) strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant S. aureus (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb S. aureus cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria.<\/jats:p>","DOI":"10.3390\/molecules27165085","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:42:56Z","timestamp":1660124576000},"page":"5085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome"],"prefix":"10.3390","volume":"27","author":[{"given":"Caroline W.","family":"Karanja","sequence":"first","affiliation":[{"name":"Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6444-9398","authenticated-orcid":false,"given":"Nimishetti","family":"Naganna","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader S.","family":"Abutaleb","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, 625 Harrison Street, West Lafayette, IN 47907, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neetu","family":"Dayal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-9747","authenticated-orcid":false,"given":"Kenneth I.","family":"Onyedibe","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA"},{"name":"Purdue Institute of Inflammation, Immunology and Infectious Disease, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4543-1536","authenticated-orcid":false,"given":"Uma","family":"Aryal","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, 625 Harrison Street, West Lafayette, IN 47907, USA"},{"name":"Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, 625 Harrison Street, West Lafayette, IN 47907, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman O.","family":"Sintim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA"},{"name":"Purdue Institute of Inflammation, Immunology and Infectious Disease, West Lafayette, IN 47907, USA"},{"name":"Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.4155\/fmc-2020-0046","article-title":"Multiple ways to kill bacteria via inhibiting novel cell wall or membrane targets","volume":"12","author":"Naclerio","year":"2020","journal-title":"Future Med. 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