{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:28:05Z","timestamp":1792794485787,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EPSTC DTP award to the University of Strathclyde","award":["EP\/T517938\/1"],"award-info":[{"award-number":["EP\/T517938\/1"]}],"id":[{"id":"https:\/\/ror.org\/00n3w3b69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"EPSTC DTP award to the University of Strathclyde","award":["2432483"],"award-info":[{"award-number":["2432483"]}],"id":[{"id":"https:\/\/ror.org\/00n3w3b69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acanthamoeba spp. is the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Strathclyde minor groove binders (S-MGBs) are a promising new class of anti-infective agent that have been shown to be effective against many infectious organisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To synthesize and evaluate the anti-Acanthamoeba activity of a panel of S-MGBs, and therefore determine the potential of this class for further development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A panel of 12 S-MGBs was synthesized and anti-Acanthamoeba activity was determined using an alamarBlue\u2122-based trophocidal assay against Acanthamoeba castellanii. Cross-screening against Trypanosoma brucei brucei, Staphylococcus aureus and Escherichia coli was used to investigate selective potency. Cytotoxicity against HEK293 cells allowed for selective toxicity to be measured. DNA binding studies were carried out using native mass spectrometry and DNA thermal shift assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>S-MGB-241 has an IC50 of 6.6 \u00b5M against A. castellanii, comparable to the clinically used miltefosine (5.6 \u00b5M) and negligible activity against the other organisms. It was also found to have an IC50\u200a&amp;gt;\u200a100 \u00b5M against HEK293 cells, demonstrating low cytotoxicity. S-MGB-241 binds to DNA as a dimer, albeit weakly compared to other S-MGBs previously studied. This was confirmed by DNA thermal shift assay with a \u0394Tm\u200a=\u200a1\u200a\u00b1\u200a0.1\u00b0C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, these data provide confidence that S-MGBs can be further optimized to generate new, potent treatments for Acanthameoba spp. infections. In particular, S-MGB-241, has been identified as a \u2018hit\u2019 compound that is selectively active against A. castellanii, providing a starting point from which to begin optimization of DNA binding and potency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkae221","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T18:26:42Z","timestamp":1718735202000},"page":"2251-2258","source":"Crossref","is-referenced-by-count":4,"title":["Strathclyde minor groove binders (S-MGBs) with activity against\n                    <i>Acanthamoeba castellanii<\/i>"],"prefix":"10.1093","volume":"79","author":[{"given":"Leah M C","family":"Mcgee","sequence":"first","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemao G","family":"Carpinteyro Sanchez","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Perieteanu","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveh","family":"Eskandari","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Mackie","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Young","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Beveridge","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J","family":"Suckling","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W","family":"Roberts","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-3698","authenticated-orcid":false,"given":"Fraser J","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pure and Applied Chemistry, University of Strathclyde , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"2024090302264413200_dkae221-B1","doi-asserted-by":"crossref","first-page":"1147077","DOI":"10.3389\/fmicb.2023.1147077","article-title":"Biological characteristics and pathogenicity of Acanthamoeba","volume":"14","author":"Wang","year":"2023","journal-title":"Front Microbiol"},{"key":"2024090302264413200_dkae221-B2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/med.21851","article-title":"Applications of medicinal chemistry for drug discovery against Acanthamoeba infections","volume":"42","author":"Ahmed","year":"2022","journal-title":"Med Res Rev"},{"key":"2024090302264413200_dkae221-B3","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.3390\/diagnostics13162655","article-title":"Diagnosis of Acanthamoeba keratitis: past, present and future","volume":"13","author":"Azzopardi","year":"2023","journal-title":"Diagnostics"},{"key":"2024090302264413200_dkae221-B4","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1007\/s11684-021-0865-2","article-title":"Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease","volume":"15","author":"Zhang","year":"2021","journal-title":"Front Med"},{"key":"2024090302264413200_dkae221-B5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3390\/pathogens9050405","article-title":"Drug discovery against Acanthamoeba infections: present knowledge and unmet needs","volume":"9","author":"Elsheikha","year":"2020","journal-title":"Pathogens"},{"key":"2024090302264413200_dkae221-B6","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/cts.12955","article-title":"Drugs used for the treatment of cerebral and disseminated infections caused by free-living amoebae","volume":"14","author":"Taravaud","year":"2021","journal-title":"Clin Transl Sci"},{"key":"2024090302264413200_dkae221-B7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.clae.2017.12.017","article-title":"Acanthamoeba in the eye, can the parasite hide even more? Latest developments on the disease","volume":"41","author":"Ju\u00e1rez","year":"2017","journal-title":"Cont Lens Anterior Eye"},{"key":"2024090302264413200_dkae221-B8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ajo.2009.06.009","article-title":"Acanthamoeba keratitis: diagnosis and treatment update","volume":"148","author":"Dart","year":"2009","journal-title":"Am J Ophthalmol"},{"key":"2024090302264413200_dkae221-B9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ajo.2020.09.048","article-title":"Oral miltefosine as salvage therapy for refractory Acanthamoeba keratitis","volume":"223","author":"Thulasi","year":"2021","journal-title":"Am J Ophthalmol"},{"key":"2024090302264413200_dkae221-B10","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/jac\/dkac001","article-title":"Intranasally administered S-MGB-364 displays antitubercular activity and modulates the host immune response to Mycobacterium tuberculosis infection","volume":"77","author":"Kieswetter","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2024090302264413200_dkae221-B11","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1021\/acs.jmedchem.8b01847","article-title":"Novel minor groove binders cure animal African trypanosomiasis in an in vivo mouse model","volume":"62","author":"Giordani","year":"2019","journal-title":"J Med Chem"},{"key":"2024090302264413200_dkae221-B12","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ejmech.2017.05.039","article-title":"An evaluation of minor groove binders as anti-fungal and anti-mycobacterial therapeutics","volume":"136","author":"Scott","year":"2017","journal-title":"Eur J Med Chem"},{"key":"2024090302264413200_dkae221-B13","doi-asserted-by":"crossref","first-page":"5343","DOI":"10.1016\/j.ejmech.2011.08.035","article-title":"Amide isosteres in structure-activity studies of antibacterial minor groove binders","volume":"46","author":"Khalaf","year":"2011","journal-title":"Eur J Med Chem"},{"key":"2024090302264413200_dkae221-B14","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1021\/acsinfecdis.2c00445","article-title":"Insights into the spectrum of activity and mechanism of action of MGB-BP-3","volume":"8","author":"Hind","year":"2022","journal-title":"ACS Infect Dis"},{"key":"2024090302264413200_dkae221-B15","doi-asserted-by":"crossref","first-page":"FDD73","DOI":"10.4155\/fdd-2022-0001","article-title":"Multitargeted anti-infective drugs: resilience to resistance in the antimicrobial resistance era","volume":"4","author":"Suckling","year":"2022","journal-title":"Future Drug Discovery"},{"key":"2024090302264413200_dkae221-B16","article-title":"Novel antibiotic mode of action by repression of promoter isomerisation","author":"Kerr","year":"2021","journal-title":"BioRxiv"},{"key":"2024090302264413200_dkae221-B17","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3390\/antibiotics11070935","article-title":"Synthesis and evaluation of novel DNA minor groove binders as antiamoebic agents","volume":"11","author":"Alniss","year":"2022","journal-title":"Antibiotics"},{"key":"2024090302264413200_dkae221-B18","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1039\/D1MD00110H","article-title":"Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype","volume":"12","author":"Brooke","year":"2021","journal-title":"RSC Med Chem"},{"key":"2024090302264413200_dkae221-B19","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/JCM.43.2.629-634.2005","article-title":"Development of colorimetric microtiter plate assay for assessment of antimicrobials against acanthamoeba","volume":"43","author":"McBride","year":"2005","journal-title":"J Clin Microbiol"},{"key":"2024090302264413200_dkae221-B20","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1021\/jm031089x","article-title":"Distamycin analogues with enhanced lipophilicity: synthesis and antimicrobial activity","volume":"47","author":"Khalaf","year":"2004","journal-title":"J Med Chem"},{"key":"2024090302264413200_dkae221-B21","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1039\/D2CB00159D","article-title":"Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy","volume":"3","author":"Tentellino","year":"2022","journal-title":"RSC Chem Bio"},{"key":"2024090302264413200_dkae221-B22","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1093\/jac\/dkx326","article-title":"Evaluation of minor groove binders (MGBs) as novel anti-mycobacterial agents and the effect of using non-ionic surfactant vesicles as a delivery system to improve their efficacy","volume":"72","author":"Hlaka","year":"2017","journal-title":"J Antimicrob Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/9\/2251\/58998575\/dkae221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/9\/2251\/58998575\/dkae221.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T22:27:32Z","timestamp":1725316052000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/9\/2251\/7709966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,7,9]]},"published-print":{"date-parts":[[2024,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae221","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,9]]},"published":{"date-parts":[[2024,7,9]]}}}