{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:44:02Z","timestamp":1760150642347,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009473","name":"I Plan Propio of the University of Malaga (UMA)","doi-asserted-by":"publisher","award":["B1-2021_08","UMA20 FEDERJA84","RTI2018-098296-BI00"],"award-info":[{"award-number":["B1-2021_08","UMA20 FEDERJA84","RTI2018-098296-BI00"]}],"id":[{"id":"10.13039\/100009473","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and\/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.<\/jats:p>","DOI":"10.3390\/md21120637","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:55:16Z","timestamp":1702457716000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["n-Tuples on Scaffold Diversity Inspired by Drug Hybridisation to Enhance Drugability: Application to Cytarabine"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-2648","authenticated-orcid":false,"given":"Miguel","family":"Garc\u00eda-Castro","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6888-0847","authenticated-orcid":false,"given":"David","family":"Fuentes-Rios","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2422-655X","authenticated-orcid":false,"given":"J. Manuel","family":"L\u00f3pez-Romero","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0812-895X","authenticated-orcid":false,"given":"Antonio","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-7852","authenticated-orcid":false,"given":"Federico","family":"Moya-Utrera","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-7933","authenticated-orcid":false,"given":"Amelia","family":"D\u00edaz-Morilla","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5149-3576","authenticated-orcid":false,"given":"Francisco","family":"Sarabia","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos s\/n, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1038\/ncomms7516","article-title":"De novo branching cascades for structural and functional diversity in small molecules","volume":"6","author":"Kremer","year":"2015","journal-title":"Nat. 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