{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:17:49Z","timestamp":1780719469849,"version":"3.54.1"},"reference-count":77,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology &amp; Innovation, Malaysia","award":["09-05-IFN-BPH-001"],"award-info":[{"award-number":["09-05-IFN-BPH-001"]}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2017\/SKK12\/USM\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2017\/SKK12\/USM\/02\/1"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dibutyl phthalate (DBP) produced by Streptomyces sp. H11809 exerted inhibitory activity against human GSK-3\u03b2 (Hs GSK-3\u03b2) and Plasmodiumfalciparum 3D7 (Pf 3D7) malaria parasites. The current study aimed to determine DBP\u2019s plausible mode of action against Hs GSK-3\u03b2 and Pf 3D7. Molecular docking analysis indicated that DBP has a higher binding affinity to the substrate-binding site (pocket 2; \u22126.9 kcal\/mol) than the ATP-binding site (pocket 1; \u22126.1 kcal\/mol) of Hs GSK-3\u03b2. It was suggested that the esters of DBP play a pivotal role in the inhibition of Hs GSK-3\u03b2 through the formation of hydrogen bonds with Arg96\/Glu97 amino acid residues in pocket 2. Subsequently, an in vitro Hs GSK-3\u03b2 enzymatic assay revealed that DBP inhibits the activity of Hs GSK-3\u03b2 via mixed inhibition inhibitory mechanisms, with a moderate IC50 of 2.0 \u00b5M. Furthermore, the decrease in Km value with an increasing DBP concentration suggested that DBP favors binding on free Hs GSK-3\u03b2 over its substrate-bound state. However, the antimalarial mode of action of DBP remains unknown since the generation of a Pf 3D7 DBP-resistant clone was not successful. Thus, the molecular target of DBP might be indispensable for Pf survival. We also identified nocardamine as another active compound from Streptomyces sp. H11809 chloroform extract. It showed potent antimalarial activity with an IC50 of 1.5 \u03bcM, which is ~10-fold more potent than DBP, but with no effect on Hs GSK-3\u03b2. The addition of \u226512.5 \u00b5M ferric ions into the Pf culture reduced nocardamine antimalarial activity by 90% under in vitro settings. Hence, the iron-chelating ability of nocardamine was shown to starve the parasites from their iron source, eventually inhibiting their growth.<\/jats:p>","DOI":"10.3390\/molecules27072292","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:34:29Z","timestamp":1648762469000},"page":"2292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Bioactivities and Mode of Actions of Dibutyl Phthalates and Nocardamine from Streptomyces sp. H11809"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-0565","authenticated-orcid":false,"given":"Fauze","family":"Mahmud","sequence":"first","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor 11800, Malaysia"},{"name":"Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngit Shin","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-3736","authenticated-orcid":false,"given":"Siew Eng","family":"How","sequence":"additional","affiliation":[{"name":"Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jualang Azlan","family":"Gansau","sequence":"additional","affiliation":[{"name":"Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-005X","authenticated-orcid":false,"given":"Khairul Mohd Fadzli","family":"Mustaffa","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0849-428X","authenticated-orcid":false,"given":"Chiuan Herng","family":"Leow","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnah","family":"Osman","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasidah Mohd","family":"Sidek","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Embi","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4280-0829","authenticated-orcid":false,"given":"Ping-Chin","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia"},{"name":"Biotechnology Research Institute, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13870","DOI":"10.1038\/s41598-020-69786-2","article-title":"Actinobacteria from Antarctica as a source for anticancer discovery","volume":"10","author":"Silva","year":"2020","journal-title":"Sci. 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