{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:37Z","timestamp":1760146957099,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The rapid evolution of bacterial resistance and the high cost of drug development have attributed greatly to the dearth in drug design. Computational approaches and natural product exploitation offer potential solutions to accelerate drug discovery. Methods: In this research article, we aimed to identify novel antibacterial hits. For the in silico studies, molecular scaffolds from the in-house chemical library of the Department of Pharmacy of Athens (Pharmalab) and the National Cancer Institute (NCI) were screened and selected for further experimental procedures. Compounds from both libraries that were not previously screened for their antimicrobial properties were tested in vitro against Gram-positive and Gram-negative bacterial strains. The microdilution method was used to determine the minimum inhibitory concentrations (MICs). Results: In silico screening identified twenty promising molecules from the NCI and seven from the Pharmalab databases. The unexplored compounds for their antibacterial activity can be characterized as weak strain-specific antimicrobials. The NSC 610491 and NSC 610493 were active against Staphylococcus aureus (MIC: 25 and 12.5 \u00b5g\/mL, respectively) and methicillin-resistant S. aureus (MRSA) (MIC: 50 and 12.5 \u00b5g\/mL, respectively). Six out of seven hydroxytyrosol (HTy) compounds were moderately active (MIC: 25\u201350 \u00b5g\/mL) against S. aureus, MRSA and Enterococcus faecalis. For the Gram-negative bacteria, no activity was detected (\u2265100 \u00b5g\/mL). Conclusions: The tested scaffolds could be considered as promising candidates for novel antimicrobials with improvements. Further experimentation is required to assess mechanisms of action and evaluate the efficacy and safety.<\/jats:p>","DOI":"10.3390\/antibiotics14010011","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T04:10:23Z","timestamp":1735618223000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Towards New Scaffolds for Antimicrobial Activity\u2014In Silico\/In Vitro Workflow Introducing New Lead Compounds"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria","family":"Mangana","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2820-9338","authenticated-orcid":false,"given":"George","family":"Lambrinidis","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9901-5223","authenticated-orcid":false,"given":"Ioannis K.","family":"Kostakis","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioanna","family":"Kalpaktsi","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-6658","authenticated-orcid":false,"given":"Marina","family":"Sagnou","sequence":"additional","affiliation":[{"name":"Institute of Biosciences & Application, NCSR \u201cDemokritos\u201d, 15310 Athens, Greece"},{"name":"Department of Science and Mathematics, Deree-The American College of Greece, 15342 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrysoula","family":"Nicolaou","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-5169","authenticated-orcid":false,"given":"Emmanuel","family":"Mikros","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-8355","authenticated-orcid":false,"given":"Stylianos","family":"Chatzipanagiotou","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Athens Medical School, Aeginition Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-7366","authenticated-orcid":false,"given":"Anastasios","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"Department of Nursing, Faculty of Health Sciences, University of Peloponnese, 22100 Tripolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"GBD 2021 Antimicrobial Resistance Collaborators. 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