{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:25:42Z","timestamp":1792211142425,"version":"4.4.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Mycetoma is a devastating neglected tropical infection of the subcutaneous tissues. It is caused by fungal and bacterial pathogens recognized as eumycetoma and actinomycetoma, respectively. Mycetoma treatment involves diagnosing the causative microorganism as a prerequisite to prescribing a proper medication. Current therapy of fungal eumycetoma causative agents, such as\n              <jats:italic>Madurella mycetomatis<\/jats:italic>\n              , consists of long-term antifungal medication with itraconazole followed by surgery, yet with usually unsatisfactory clinical outcomes. Actinomycetoma, on the contrary, usually responds to treatment with co-trimoxazole and amikacin. Therefore, there is a pressing need to discover novel broad-spectrum antimicrobial agents to circumvent the time-consuming and costly diagnosis. Using the resazurin assay, a series of 23 naphthylisoquinoline (NIQ) alkaloids and related naphthoquinones were subjected to\n              <jats:italic>in vitro<\/jats:italic>\n              screening against two fungal strains of\n              <jats:italic>M. mycetomatis<\/jats:italic>\n              and three bacterial strains of\n              <jats:italic>Actinomadura madurae<\/jats:italic>\n              and\n              <jats:italic>A. syzygii<\/jats:italic>\n              . Seven NIQs, mostly dimers, showed promising\n              <jats:italic>in vitro<\/jats:italic>\n              activities against at least one strain of the mycetoma-causative pathogens, while the naphthoquinones did not show any activity. A synthetic NIQ dimer, 8,8'''-\n              <jats:italic>O<\/jats:italic>\n              ,\n              <jats:italic>O<\/jats:italic>\n              -dimethylmichellamine A (\n              <jats:bold>18<\/jats:bold>\n              ), inhibited all tested fungal and bacterial strains (IC\n              <jats:sub>50<\/jats:sub>\n              <jats:strike>=<\/jats:strike>\n              2.81\u201312.07 \u00b5g\/mL). One of the dimeric NIQs, michellamine B (\n              <jats:bold>14<\/jats:bold>\n              ), inhibited a strain of\n              <jats:italic>M. mycetomatis<\/jats:italic>\n              and significantly enhanced the survival rate of\n              <jats:italic>Galleria mellonella<\/jats:italic>\n              larvae infected with\n              <jats:italic>M. mycetomatis<\/jats:italic>\n              at concentrations of 1 and 4 \u00b5g\/mL, without being toxic to the uninfected larvae. As a result, broad-spectrum dimeric NIQs like\n              <jats:bold>14<\/jats:bold>\n              and\n              <jats:bold>18<\/jats:bold>\n              with antimicrobial activity are considered hit compounds that could be worth further optimization to develop novel lead antimycetomal agents.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01612-23","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T13:00:28Z","timestamp":1712840428000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Naphthylisoquinoline alkaloids: novel agents against the causative pathogens of eumycetoma and actinomycetoma\u2014\n            <i>en route<\/i>\n            to broad-spectrum antimycetomal drugs"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2511-7040","authenticated-orcid":false,"given":"Sami Ahmed","family":"Khalid","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Science and Technology, Omdurman, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-6909","authenticated-orcid":false,"given":"Shereen","family":"Abd Algaffar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Science and Technology, Omdurman, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1901-3824","authenticated-orcid":false,"given":"Nasir","family":"Tajuddeen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaise Kimbadi","family":"Lombe","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Faculty of Sciences, University of Kinshasa, Kinshasa, Democratic Republic of the Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-5935","authenticated-orcid":false,"given":"Gerhard","family":"Bringmann","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002550"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232556"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myx061"},{"key":"e_1_3_4_5_2","unstructured":"69th World health assembly A69\/35 provisional agenda item 15.3. 2016. 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