{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:23:39Z","timestamp":1787315019291,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Doctoral Fund of Kaunas University of Technology","award":["A-410"],"award-info":[{"award-number":["A-410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increasing antimicrobial resistance among Gram-positive pathogens and pathogenic fungi remains one of the major public healthcare threats. Therefore, novel antimicrobial candidates and scaffolds are critically needed to overcome resistance in Gram-positive pathogens and drug-resistant fungal pathogens. In this study, we explored 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid and its 3,5-dichloro-2-hydroxyphenyl analogue for their in vitro antimicrobial activity against multidrug-resistant pathogens. The compounds showed structure-dependent antimicrobial activity against Gram-positive pathogens (S. aureus, E. faecalis, C. difficile). Compounds 14 and 24b showed promising activity against vancomycin-intermediate S. aureus strains, and favorable cytotoxic profiles in HSAEC-1 cells, making them attractive scaffolds for further development. 5-Fluorobenzimidazole, having a 3,5-dichloro-2-hydroxyphenyl substituent, was found to be four-fold, and hydrazone, with a thien-2-yl fragment, was two-fold stronger than clindamycin against methicillin resistant S. aureus TCH 1516. Moreover, hydrazone, bearing a 5-nitrothien-2-yl moiety, showed promising activity against three tested multidrug-resistant C. auris isolates representing major genetic lineages (MIC 16 \u00b5g\/mL) and azole-resistant A. fumigatus strains harboring TR34\/L98H mutations in the CYP51A gene. The anticancer activity characterization demonstrated that the 5-fluorobenzimidazole derivative with a 3,5-dichloro-2-hydroxyphenyl substituent showed the highest anticancer activity in an A549 human pulmonary cancer cell culture model. Collectively these results demonstrate that 1-(2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives could be further explored for the development of novel candidates targeting Gram-positive pathogens and drug-resistant fungi.<\/jats:p>","DOI":"10.3390\/ijms24097966","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T02:27:56Z","timestamp":1682648876000},"page":"7966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis of 1-(2-Hydroxyphenyl)- and (3,5-Dichloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives as Promising Scaffolds for the Development of Novel Antimicrobial and Anticancer Agents"],"prefix":"10.3390","volume":"24","author":[{"given":"Monika","family":"Berta\u0161i\u016bt\u0117","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Rd. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0237-9088","authenticated-orcid":false,"given":"Povilas","family":"Kavaliauskas","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Rd. 19, 50254 Kaunas, Lithuania"},{"name":"Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA"},{"name":"Institute for Genome Sciences, School of Medicine, University of Maryland Baltimore School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA"},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology, Bir\u0161tono Str. 38A, 59116 Prienai, Lithuania"},{"name":"Biological Research Center, Lithuanian University of Health Sciences, Til\u017e\u0117s St. 18, 47181 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Vaickelionien\u0117","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Rd. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birut\u0117","family":"Grybait\u0117","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Rd. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6811-4467","authenticated-orcid":false,"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA"},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology, Bir\u0161tono Str. 38A, 59116 Prienai, Lithuania"},{"name":"Biological Research Center, Lithuanian University of Health Sciences, Til\u017e\u0117s St. 18, 47181 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-8058","authenticated-orcid":false,"given":"R\u016bta","family":"Petraitien\u0117","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA"},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology, Bir\u0161tono Str. 38A, 59116 Prienai, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Naing","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Garcia","sequence":"additional","affiliation":[{"name":"Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u016brat\u0117","family":"\u0160iug\u017edait\u0117","sequence":"additional","affiliation":[{"name":"Department of the Veterinary Pathobiology, Lithuanian University of Health Science, Til\u017e\u0117s St. 18, 47181 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundas","family":"Lele\u0161ius","sequence":"additional","affiliation":[{"name":"Department of the Veterinary Pathobiology, Lithuanian University of Health Science, Til\u017e\u0117s St. 18, 47181 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-2941","authenticated-orcid":false,"given":"Vytautas","family":"Mickevi\u010dius","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Rd. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vazquez-Guillamet, C., and Kollef, M.H. 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