{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:26:47Z","timestamp":1777444007753,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T00:00:00Z","timestamp":1344988800000},"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>Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for in vitro antimicrobial and cytotoxic activities. A number of congeners exhibited antimicrobial activity against a range of Gram-positive bacteria including Mycobacterium tuberculosis H37Rv, with four displaying notable antitubercular activity against both replicating and non-replicating persistent forms of M. tuberculosis. One new semi-synthetic compound, 21-((1H-imidazol-5-yl)methyl)-pseudopteroxazole (7a), was more potent than the natural products pseudopterosin and pseudopteroxazole and exhibited equipotent activity against both replicating and non-replicating persistent forms of M. tuberculosis with a near absence of in vitro cytotoxicity. Pseudopteroxazole also exhibited activity against strains of M. tuberculosis H37Rv resistant to six clinically used antibiotics.<\/jats:p>","DOI":"10.3390\/md10081711","type":"journal-article","created":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T11:05:46Z","timestamp":1345028746000},"page":"1711-1728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against Mycobacterium tuberculosis and Other Pathogens"],"prefix":"10.3390","volume":"10","author":[{"given":"Malcolm W. B.","family":"McCulloch","sequence":"first","affiliation":[{"name":"Department of Chemistry and Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad","family":"Haltli","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada"},{"name":"Nautilus Biosciences Canada, Inc., Charlottetown, PEI C1A 4P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas H.","family":"Marchbank","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell G.","family":"Kerr","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada"},{"name":"Nautilus Biosciences Canada, Inc., Charlottetown, PEI C1A 4P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,8,15]]},"reference":[{"key":"ref_1","unstructured":"(2011). The Global Plan to Stop TB 2011\u20132015: Transforming the Fight towards Elimination of Tuberculosis, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.4155\/fmc.11.115","article-title":"Challenges and opportunities in developing novel drugs for TB","volume":"3","author":"Kaneko","year":"2011","journal-title":"Future Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09657","article-title":"The Challenge of new drug discovery for tuberculosis","volume":"469","author":"Koul","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6157","DOI":"10.1021\/jm200305q","article-title":"Current status and research strategies in tuberculosis drug development","volume":"54","author":"Dover","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.4155\/fmc.09.113","article-title":"Natural product scaffolds as leads to drugs","volume":"1","author":"Newman","year":"2009","journal-title":"Future Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1021\/ol9907116","article-title":"Novel antimycobacterial benzoxazole alkaloids, from the west Indian Sea whip Pseudopterogorgia elisabethae","volume":"1","author":"Rodriguez","year":"1999","journal-title":"Org. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1021\/np030052c","article-title":"Homopseudopteroxazole, a new antimycobacterial diterpene alkaloid from Pseudopterogorgia elisabethae","volume":"66","author":"Rodriguez","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1021\/ol0515412","article-title":"Benzothiazines in synthesis. A total synthesis of pseudopteroxazole","volume":"7","author":"Harmata","year":"2005","journal-title":"Org. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1021\/jo9009112","article-title":"Benzothiazines in synthesis. A formal total synthesis of pseudopteroxazole","volume":"74","author":"Harmata","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13486","DOI":"10.1021\/ja0378916","article-title":"First enantiospecific total synthesis of the antitubercular marine natural product pseudopteroxazole. Revision of assigned stereochemistry","volume":"125","author":"Davidson","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1021\/np2006555","article-title":"One-pot syntheses of pseudopteroxazoles from pseudopterosins: A rapid route to non-natural congeners with improved antimicrobial activity","volume":"74","author":"McCulloch","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_12","unstructured":"More than 26 different pseudopterosins have been identified in nature, these can possess different configurations about the aglycone and\/or different sugars."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1016\/j.bmc.2011.06.083","article-title":"Marine diterpene glycosides","volume":"19","author":"Berrue","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6238","DOI":"10.1073\/pnas.83.17.6238","article-title":"The pseudopterosins: Anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae","volume":"83","author":"Look","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1021\/np049802o","article-title":"New pseudopterosin and seco-pseudopterosin diterpene glycosides from two Colombian isolates of Pseudopterogorgia elisabethae and their diverse biological activities","volume":"67","author":"Rodriguez","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3390\/md9030334","article-title":"Cytotoxic and antimicrobial activity of pseudopterosins and seco-pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andres and Providencia Islands (Southwest Caribbean Sea)","volume":"9","author":"Correa","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/hlca.200490099","article-title":"New antibacterial diterpenes from Pseudopterogorgia elisabethae","volume":"87","author":"Ata","year":"2004","journal-title":"Helv. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1021\/ol006192k","article-title":"Syntheses and stereochemical revision of pseudopterosin G\u2013J aglycon and helioporin E","volume":"2","author":"Lazerwith","year":"2000","journal-title":"Org. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1021\/jo00303a030","article-title":"New anti-inflammatory pseudopterosins from the marine octocoral Pseudopterogorgia elisabethae","volume":"55","author":"Roussis","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/JCM.36.2.362-366.1998","article-title":"Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay","volume":"36","author":"Franzblau","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1128\/AAC.49.4.1447-1454.2005","article-title":"In vitro and in vivo activities of macrolide derivatives against Mycobacterium tuberculosis","volume":"49","author":"Falzari","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1128\/AAC.00055-06","article-title":"Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis","volume":"51","author":"Cho","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1128\/AAC.41.5.1004","article-title":"Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium  avium","volume":"41","author":"Collins","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1021\/np2000667","article-title":"Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens","volume":"74","author":"Lankin","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1590\/S1806-37132010000500017","article-title":"Antituberculosis drugs: Drug interactions, adverse effects, and use in special situations. Part 2: Second line drugs","volume":"36","author":"Arbex","year":"2010","journal-title":"J. Bras. Pneumol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2174\/138955707782331740","article-title":"Overview of anti-tuberculosis (TB) drugs and their resistance mechanisms","volume":"7","author":"Shi","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.tube.2010.09.002","article-title":"Evaluation of the Mycobacterium smegmatis and BCG models for the discovery of Mycobacterium tuberculosis inhibitors","volume":"90","author":"Altaf","year":"2010","journal-title":"Tuberculosis (Edinb.)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1016\/j.tet.2011.03.006","article-title":"Semisynthesis of fuscoside B analogues and eunicosides, and analysis of anti-inflammatory activity","volume":"67","author":"Marchbank","year":"2011","journal-title":"Tetrahedron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1021\/ol030084r","article-title":"Sugar\/steroid\/sugar conjugates: Sensitivity of lipid binding to sugar structure","volume":"5","author":"Mbadugha","year":"2003","journal-title":"Org. Lett."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/10\/8\/1711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:51:48Z","timestamp":1760219508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/10\/8\/1711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,15]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2012,8]]}},"alternative-id":["md10081711"],"URL":"https:\/\/doi.org\/10.3390\/md10081711","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,15]]}}}