{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:39:05Z","timestamp":1787585945343,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2010,2,23]],"date-time":"2010-02-23T00:00:00Z","timestamp":1266883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC50 &lt; 0.11 \u00b5M; staurosporine IC50 5.30 \u00b5M) and Trypanosoma brucei brucei (valinomycin IC50 0.0032 \u00b5M; staurosporine IC50 0.022 \u00b5M; butenolide IC50 31.77 \u00b5M). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities.<\/jats:p>","DOI":"10.3390\/md8020373","type":"journal-article","created":{"date-parts":[[2010,2,23]],"date-time":"2010-02-23T11:22:12Z","timestamp":1266924132000},"page":"373-380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Anti-Parasitic Compounds from Streptomyces sp. Strains Isolated from Mediterranean Sponges"],"prefix":"10.3390","volume":"8","author":[{"given":"Sheila Marie","family":"Pimentel-Elardo","sequence":"first","affiliation":[{"name":"Julius-von-Sachs Institute for Biological Sciences, University of W\u00fcrzburg, Julius-von-Sachs Platz 3, 97082 W\u00fcrzburg, Germany"},{"name":"Research Center for Infectious Diseases, Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana","family":"Kozytska","sequence":"additional","affiliation":[{"name":"Research Center for Infectious Diseases, Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim S.","family":"Bugni","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Utah, Salt Lake City, 84112 Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris M.","family":"Ireland","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Utah, Salt Lake City, 84112 Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Moll","sequence":"additional","affiliation":[{"name":"Research Center for Infectious Diseases, Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Julius-von-Sachs Institute for Biological Sciences, University of W\u00fcrzburg, Julius-von-Sachs Platz 3, 97082 W\u00fcrzburg, Germany"},{"name":"Research Center for Infectious Diseases, Josef-Schneider-Stra\u00dfe 2, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2010,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10482-004-6540-1","article-title":"Marine actinomycete diversity and natural product discovery","volume":"87","author":"Jensen","year":"2005","journal-title":"Anton Leeuwenhoek"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.tim.2007.10.004","article-title":"Marine actinobacteria: New opportunities for natural product search and discovery","volume":"15","author":"Bull","year":"2007","journal-title":"Trends Microbiol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nchembio841","article-title":"Developing a new resource for drug discovery: Marine actinomycete bacteria","volume":"2","author":"Fenical","year":"2006","journal-title":"Nat Chem Biol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1128\/AEM.68.10.5005-5011.2002","article-title":"Widespread and persistent populations of a major new marine actinomycete taxon in ocean sediments","volume":"68","author":"Mincer","year":"2002","journal-title":"Appl Environ Microbiol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10482-004-6525-0","article-title":"Diversity of culturable actinobacteria in geographically widespread marine sediments","volume":"87","author":"Maldonado","year":"2005","journal-title":"Anton Leeuwenhoek"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1462-2920.2005.00716.x","article-title":"Marine actinomycetes related to the \u201cSalinospora\u201d group from the Great Barrier Reef sponge Pseudoceratina clavata","volume":"7","author":"Kim","year":"2005","journal-title":"Environ 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Leeuwenhoek"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10482-007-9169-z","article-title":"Diversity of culturable actinobacteria isolated from marine sponge Haliclona sp","volume":"92","author":"Jiang","year":"2007","journal-title":"Anton Leeuwenhoek"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6820","DOI":"10.1128\/AEM.01238-09","article-title":"Microhabitats within venomous cone snails contain diverse actinobacteria","volume":"75","author":"Peraud","year":"2009","journal-title":"Appl Environ Microbiol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.mib.2006.03.004","article-title":"Discovery of novel metabolites from marine actinomycetes","volume":"9","author":"Lam","year":"2006","journal-title":"Curr Opin Microbiol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.5670\/oceanog.2006.74","article-title":"Marine pharmaceuticals: past, present and future","volume":"19","author":"Fenical","year":"2006","journal-title":"Oceanography"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ijantimicag.2007.01.004","article-title":"Leishmania spp.: Proficiency of drug-resistant parasites","volume":"29","author":"Natera","year":"2007","journal-title":"Int J Antimicrob Agents"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1099\/ijs.0.007856-0","article-title":"Streptomyces axinellae sp. nov., isolated from the Mediterranean sponge Axinella polypoides (Porifera)","volume":"59","author":"Scheuermayer","year":"2009","journal-title":"Int J Syst Evol Microbiol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1099\/ijs.0.64971-0","article-title":"Saccharopolyspora cebuensis sp. nov., a novel actinomycete isolated from a Philippine sponge (Porifera)","volume":"58","author":"Tiro","year":"2008","journal-title":"Int J Syst Evol Microbiol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.1016\/j.tetlet.2008.09.094","article-title":"Cebulactams A1 and A2, new macrolactams isolated from Saccharopolyspora cebuensis, the first obligate-marine strain of the genus Saccharopolyspora","volume":"49","author":"Gulder","year":"2008","journal-title":"Tetrahedron Lett"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3354\/ame033239","article-title":"Isolation of planctomycetes from Aplysina sponges","volume":"33","author":"Wehrl","year":"2003","journal-title":"Aquat Microb Ecol"},{"key":"ref_19","unstructured":"The isolation of valinomycin was carried out by semi-preparative HPLC (Phenomenex Luna SemiPrep RP18e 10 \u00d7 250 mm) using H2O (A) and CH3OH (B) as the solvents and the following gradient: flow 4.5 mL\/min; 0\u20135 min 90% B, 11\u201315 min 100% B yielding 8.4 mg of the compound (Rt = 13.085 min)."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/cber.19550880111","article-title":"Valinomycin I, XXVII. Mitteilung \u00fcber Antibiotika aus Actinomyceten","volume":"88","author":"Brockmann","year":"1955","journal-title":"Chem Ber"},{"key":"ref_21","unstructured":"Leishmania major promastigotes were seeded at a cell density of 1 \u00d7 107 cells\/mL into 96-well plates in complete medium (RPMI with NaHCO3, 10% FCS, 2 mM glutamine, 10 mM Hepes pH 7.2, 100 U\/mL penicillin, 50 \u03bcg\/mL gentamicin, 50 mM 2-mercaptoethanol) without phenol red (200 mL), in the absence or presence of different concentrations of the compounds. These were then incubated for 24 h at 26 \u00b0C, 5% CO2 and 95% humidity. Following the addition of 20 mL of Alamar Blue, the plates were incubated again and the optical densities (ODs) measured 24 h and 48 h later with an enzyme-linked immunosorbent assay (ELISA) reader (Multiskan Ascent, Germany) using a test wavelength of 540 nm and a reference wavelength of 630 nm. Absorbance in the absence of compounds was set as 100% of growth. Amphotericin B was used as a reference compound and positive control. The effects of cell density, incubation time and the concentration of DMSO were examined in control experiments. The final concentration of DMSO in the medium never exceeded 1% vol\/vol and had no effect on the proliferation of extracellular or intracellular parasites. For each experiment, each drug concentration was assayed in duplicate wells [31]"},{"key":"ref_22","unstructured":"Trypomastigote forms of Trypanosoma brucei brucei laboratory strain TC 221 were cultured in complete Baltz medium [80 mL Baltz medium basic solution, 0.8 mL 2 mercaptoethanol stock solution (20 mM), 0.8 mL penicillin\/streptomycin (10,000 U\/mL), 16 mL FCS (inactivated for 30 min at 56 \u00b0C). Baltz medium basic solution is composed of the following: 500 mL MEM with Earle\u2019s salts and L-glutamine, 3 g Hepes, 0.5 g monohydrate glucose, 0.110 g sodium pyruvate, 0.007 g hypoxanthine, 0.002 g thymidine, 0.0107 g adenosine, 0.0141 g bathocuproine disulfonic acid disodium salt, 0.146 g glutamine, 5 mL sterile non-essential amino acid concentrate (100\u00d7, pH 7.5). A defined number of parasites (104 trypanosomes per mL) were exposed in test chambers of 96-well plates to various concentrations of the test substances (previously dissolved in DMSO) to make a final volume of 200 \u03bcL in duplicates. Positive (trypanosomes in culture medium) and negative controls (test substance without trypanosomes) were run simultaneously with each plate. The plates were then incubated at 37 \u00b0C in an atmosphere of 5% CO2 for a total time period of 72 h. After 24 h, 20 \u03bcL of Alamar Blue was added. The activity of the test substances was measured by light absorption using MR 700 Microplate Reader at a wavelength of 550 nm with a reference wavelength of 630 nm. The first reading was done at 48 h and subsequently at 72 h. The effect of the test substances was quantified in IC50 values by linear interpolation of three independent measurements [32]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1021\/jf00084a039","article-title":"Production of valinomycin, an insecticidal antibiotic, by Streptomyces griseus var. flexipartum var. nov","volume":"36","author":"Heisey","year":"1988","journal-title":"J Agric Food Chem"},{"key":"ref_24","unstructured":"The isolation of staurosporine was carried out by semi-preparative HPLC (Phenomenex Luna SemiPrep RP18e 10 \u00d7 250 mm) using H2O + 0.1% TFA (A) and CH3OH (B) as the solvents and the following gradient: flow 4.5 mL\/min; 0\u20135 min 70% B, 10 min 80% B, 20\u201325 min 100% B to yield 1.4 mg of the compound (Rt = 4.162 min)."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1021\/np030233e","article-title":"DD-diketopiperazines: Antibiotics active against Vibrio anguillarum isolated from marine bacteria associated with cultures of Pecten maximus","volume":"66","author":"Fdhila","year":"2003","journal-title":"J Nat Prod"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1021\/np010259a","article-title":"Further new staurosporine derivatives from the ascidian Eudistoma toealensis and its predatory flatworm Pseudoceros sp","volume":"65","author":"Schupp","year":"2002","journal-title":"J Nat Prod"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/(SICI)1097-0215(19980703)77:1<64::AID-IJC11>3.0.CO;2-9","article-title":"Reversal of multidrug resistance by the staurosporine derivatives CGP 41251 and CGP 42700","volume":"77","author":"Utz","year":"1998","journal-title":"Int J Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1021\/np000599g","article-title":"New lactone-containing metabolites from a marine-derived bacterium of the genus Streptomyces","volume":"64","author":"Cho","year":"2001","journal-title":"J Nat Prod"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1021\/np0001676","article-title":"New butenolides from two marine streptomycetes","volume":"63","author":"Mukku","year":"2000","journal-title":"J Nat Prod"},{"key":"ref_30","unstructured":"J774.1 macrophages were cultured in complete medium (RPMI with NaHCO3, 10% FCS, 2 mM glutamine, 10 mM Hepes pH 7.2, 100 U\/mL penicillin, 50 \u03bcg\/mL gentamicin, 50 \u03bcM 2-mercaptoethanol) without phenol red in the absence or presence of increasing concentrations of the compounds at a cell density of 1 \u00d7 105 cells\/mL (200 \u03bcL) for 24 h at 37 \u00b0C, 5% CO2 and 95% humidity. Following the addition of 20 \u03bcL of Alamar Blue, the plates were incubated and the ODs measured at 24 h, 48 h and 72 h. The same Alamar blue assay previously described for Leishmania was followed [21]. Kidney epithelial 293T cells were also tested in the same manner as the macrophages but using complete DMEM medium (4.5 g\/L solution of DMEM high glucose solution with sodium pyruvate but without L-glutamine, FBS superior at final concentration of 20%, 200 mM L-glutamine 100x) and cell density (2 \u00d7 104 cells\/mL)."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1128\/AAC.01430-05","article-title":"Aziridine-2,3-dicarboxylates, peptidomimetic cysteine protease inhibitors with antileishmanial activity","volume":"50","author":"Vicik","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0001-706X(93)90083-N","article-title":"A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites","volume":"55","author":"Huber","year":"1993","journal-title":"Acta Trop"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/8\/2\/373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:01:32Z","timestamp":1760220092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/8\/2\/373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2,23]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2010,2]]}},"alternative-id":["md8020373"],"URL":"https:\/\/doi.org\/10.3390\/md8020373","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2,23]]}}}