{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:56:13Z","timestamp":1791302173491,"version":"4.1.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004702","name":"Universit? degli Studi di Genova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antimicrobial resistance is an urgent global public health threat, killing at least 1.27 million people worldwide and associated with nearly 5 million deaths. Antibiotic resistance has been recently recognized by the WHO as a global health emergency. In this scenario, the research and development of novel derivatives specifically active against resistant pathogens became an urgent need. Pyrazole-based compounds have recently attracted significant interest for their potential antimicrobial activity, particularly against resistant Gram-positive strains such as methicillin-resistant Staphylococcus aureus (MRSA). Based on this evidence, we carried out an in-depth investigation of this chemical class by the synthesis of unreported compounds differently decorated on the pyrazole scaffold. The newly prepared derivatives were tested on a large panel of Gram-negative and Gram-positive strains. Interestingly, pyrazolyl ureas (PUs) 1c and 1h showed excellent minimum inhibitory concentration (MIC) values (8\u201316 \u03bcg\/mL) against different Staphylococcus strains and were therefore further evaluated by minimum bactericidal concentration (MBC) determination and time-kill assays and for their ability to inhibit biofilm formation on several MRSA strains. Pyrazole 1c was shown to exert such inhibition at MIC and sub-MIC concentrations (1\/2 MIC and 1\/4 MIC), highlighting the pharmaceutical potential of this class of compounds against resistant MRSA. Finally, selected PUs did not affect GM-6114 cell viability, thus indicating the lack of cytotoxicity on healthy fibroblasts, and were predicted to possess favorable physicochemical, pharmacokinetic, and drug-likeness profiles.<\/jats:p>","DOI":"10.1021\/acsomega.6c03582","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:21:49Z","timestamp":1790086909000},"page":"58851-58861","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis,\nand Microbiological Evaluation\nof Differently Decorated Pyrazoles Able to Overcome Antimicrobial\nResistance and Biofilm Formation"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-7891","authenticated-orcid":true,"given":"Matteo","family":"Lusardi","sequence":"first","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 3 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Caviglia","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 3 , ,","place":["Genova, Italy, 16132"]},{"name":"University of Genoa , , Viale Benedetto XV, 6 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Chiocca","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 3 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ponassi","sequence":"additional","affiliation":[{"name":"UOS Proteomica e Spettrometria di Massa , , L.go. R. Benzi, 10 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Piatti","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 6 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Salis","sequence":"additional","affiliation":[{"name":"University of Genoa , , Largo Rosanna Benzi 10, PAD.3 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Spallarossa","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 3 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Schito","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 6 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7726","authenticated-orcid":true,"given":"Chiara","family":"Brullo","sequence":"additional","affiliation":[{"name":"University of Genoa , , Viale Benedetto XV, 3 , ,","place":["Genova, Italy, 16132"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"1","key":"2026100610482570800_cit1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.pop.2025.09.006","article-title":"Antibiotic Stewardship","volume":"53","author":"Epling","year":"2026","journal-title":"Primary\nCare: Clinics in Office Practice"},{"issue":"11","key":"2026100610482570800_cit2","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.cmi.2017.08.026","article-title":"What Is Antimicrobial\nStewardship?","volume":"23","author":"Dyar","year":"2017","journal-title":"Clinical Microbiology and Infection"},{"key":"2026100610482570800_cit3","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1080\/17460913.2026.2627823","article-title":"Combatting Antibiotic\nResistance: Challenges and Emerging Therapeutic Strategies","volume":"21","author":"Acharya","year":"2026","journal-title":"Future Microbiology"},{"issue":"3","key":"2026100610482570800_cit4","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3390\/molecules27030616","article-title":"Multidrug\nResistance (MDR): A Widespread Phenomenon in Pharmacological Therapies","volume":"27","author":"Catalano","year":"2022","journal-title":"Molecules"},{"issue":"20","key":"2026100610482570800_cit5","doi-asserted-by":"publisher","first-page":"8268","DOI":"10.1021\/acs.jmedchem.7b00215","article-title":"Pharmaceutical Approaches to Target Antibiotic Resistance\nMechanisms","volume":"60","author":"Schillaci","year":"2017","journal-title":"J. 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Chem."},{"issue":"6","key":"2026100610482570800_cit6","doi-asserted-by":"publisher","first-page":"488","DOI":"10.3322\/caac.21697","article-title":"Antibiotic\nResistance in the Patient with Cancer: Escalating\nChallenges and Paths Forward","volume":"71","author":"Nanayakkara","year":"2021","journal-title":"CA A Cancer J.\nClinicians"},{"issue":"2","key":"2026100610482570800_cit7","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.idc.2016.02.001","article-title":"Overview: Global and Local Impact of Antibiotic Resistance","volume":"30","author":"Watkins","year":"2016","journal-title":"Infectious Disease Clinics of North America"},{"issue":"7","key":"2026100610482570800_cit8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial\nResistance: A Global\nMultifaceted Phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathogens and Global\nHealth"},{"issue":"9","key":"2026100610482570800_cit9","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrmicro2200","article-title":"Waves of Resistance:\nStaphylococcus Aureus in the Antibiotic\nEra","volume":"7","author":"Chambers","year":"2009","journal-title":"Nat. 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Microbiol"},{"issue":"s136","key":"2026100610482570800_cit12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/apm.12099","article-title":"The Role of\nBacterial Biofilms in Chronic Infections","volume":"121","author":"Bjarnsholt","year":"2013","journal-title":"APMIS"},{"key":"2026100610482570800_cit13","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.717809","article-title":"A Review on\nOccurrence and Spread of Antibiotic Resistance in Wastewaters and\nin Wastewater Treatment Plants: Mechanisms and Perspectives","volume":"12","author":"Uluseker","year":"2021","journal-title":"Front. 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Chemother."},{"key":"2026100610482570800_cit16","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1080\/17425247.2026.2631043","article-title":"Recent and Future Developments\nin Inhaled Formulations\nto Overcome Anti-Bacterial Drug Resistance","volume":"23","author":"Islam","year":"2026","journal-title":"Expert Opinion on Drug Delivery"},{"issue":"9","key":"2026100610482570800_cit17","doi-asserted-by":"publisher","first-page":"7834","DOI":"10.3390\/ijms24097834","article-title":"Amino-Pyrazoles in Medicinal Chemistry:\nA Review","volume":"24","author":"Lusardi","year":"2023","journal-title":"IJMS"},{"issue":"12","key":"2026100610482570800_cit18","doi-asserted-by":"publisher","first-page":"2758","DOI":"10.3390\/molecules25122758","article-title":"Synthesis\nand Antimicrobial Studies\nof Coumarin-Substituted Pyrazole Derivatives as Potent Anti-Staphylococcus\nAureus Agents","volume":"25","author":"Alnufaie","year":"2020","journal-title":"Molecules"},{"issue":"1","key":"2026100610482570800_cit19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s11030-020-10046-w","article-title":"Antibacterial Evaluation\nand Molecular Docking Studies of Pyrazole\u2013Thiosemicarbazones\nand Their Pyrazole\u2013Thiazolidinone Conjugates","volume":"25","author":"Ebenezer","year":"2021","journal-title":"Mol. 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Med. Chem. Lett."},{"issue":"1","key":"2026100610482570800_cit23","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s40203-025-00534-y","article-title":"Identification of\nPotential Inhibitors Derived from\nIndole and Pyrazole against New Delhi Metallo-\u03b2-Lactamase-1\n(NDM-1)","volume":"14","author":"Kumar","year":"2026","journal-title":"In Silico Pharmacol."},{"issue":"4","key":"2026100610482570800_cit24","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.3390\/molecules28041712","article-title":"Antimalarial\nActivity of Tri- and Tetra-Substituted Anilino Pyrazoles","volume":"28","author":"Lusardi","year":"2023","journal-title":"Molecules"},{"issue":"21","key":"2026100610482570800_cit25","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.4155\/fmc-2023-0207","article-title":"Pyrazole:\nAn Emerging Privileged Scaffold in Drug Discovery","volume":"15","author":"Alam","year":"2023","journal-title":"Future Med. 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J. Med. Chem."},{"issue":"1","key":"2026100610482570800_cit31","doi-asserted-by":"publisher","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A Free Web Tool to Evaluate\nPharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness\nof Small Molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep"},{"issue":"18","key":"2026100610482570800_cit32","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1016\/S0960-894X(01)00483-8","article-title":"Synthesis\nand Biological Data of 4-Amino-1-(2-Chloro-2-Phenylethyl)-1H-Pyrazolo[3,4-b]Pyridine-5-Carboxylic\nAcid Ethyl Esters, a New Series of A1-Adenosine Receptor (A1AR) Ligands","volume":"11","author":"Schenone","year":"2001","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"14","key":"2026100610482570800_cit33","doi-asserted-by":"publisher","first-page":"6523","DOI":"10.1021\/jm3005866","article-title":"The Discovery and\nOptimization of a Novel Class of\nPotent, Selective, and Orally Bioavailable Anaplastic Lymphoma Kinase\n(ALK) Inhibitors with Potential Utility for the Treatment of Cancer","volume":"55","author":"Lewis","year":"2012","journal-title":"J. Med. Chem."},{"issue":"3","key":"2026100610482570800_cit34","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus\nAureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations,\nand Management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin Microbiol Rev."},{"issue":"8","key":"2026100610482570800_cit35","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/nrmicro2182","article-title":"Staphylococcus\nEpidermidis \u2500 the \u201caccidental\u201d Pathogen","volume":"7","author":"Otto","year":"2009","journal-title":"Nat. Rev. Microbiol"},{"issue":"2","key":"2026100610482570800_cit36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1111\/j.1574-6968.2007.00688.x","article-title":"Ica and beyond:\nBiofilm Mechanisms and Regulation in Staphylococcus Epidermidis and Staphylococcus Aureus","volume":"270","author":"O\u2019Gara","year":"2007","journal-title":"FEMS Microbiology Letters"},{"issue":"3","key":"2026100610482570800_cit37","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/s00203-025-04698-1","article-title":"Vancomycin Resistance\nin Gram-Positive Infections: Evolutionary Strategies\nof Survival","volume":"208","author":"Hu","year":"2026","journal-title":"Arch. Microbiol."},{"issue":"1","key":"2026100610482570800_cit38","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1128\/CMR.00042-09","article-title":"Reduced\nVancomycin Susceptibility in Staphylococcus Aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate\nStrains: Resistance Mechanisms, Laboratory Detection, and Clinical\nImplications","volume":"23","author":"Howden","year":"2010","journal-title":"Clin Microbiol Rev."},{"issue":"5","key":"2026100610482570800_cit39","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1177\/026119290403200503","article-title":"A Modular\nApproach to the ECVAM Principles\non Test Validity","volume":"32","author":"Hartung","year":"2004","journal-title":"Altern Lab Anim"},{"issue":"1_suppl","key":"2026100610482570800_cit40","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1177\/026119290403201s105","article-title":"The Principles of Validation\nand the ECVAM Validation Process","volume":"32","author":"Worth","year":"2004","journal-title":"Altern Lab\nAnim"},{"issue":"3","key":"2026100610482570800_cit41","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1002\/cmdc.200700139","article-title":"Lessons Learnt from\nAssembling Screening Libraries for Drug Discovery for Neglected Diseases","volume":"3","author":"Brenk","year":"2008","journal-title":"ChemMedChem."},{"issue":"3","key":"2026100610482570800_cit42","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1021\/ci034243x","article-title":"ESOL: Estimating\nAqueous Solubility Directly from Molecular Structure","volume":"44","author":"Delaney","year":"2004","journal-title":"J. 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