{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:19:23Z","timestamp":1764494363744,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"],"award-info":[{"award-number":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"],"award-info":[{"award-number":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"]}]},{"name":"FEDER","award":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"],"award-info":[{"award-number":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"]}]},{"name":"BEAP-MAR","award":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"],"award-info":[{"award-number":["UIDP\/04292\/2020","LA\/P\/0069\/2020","2022.09196.PTDC","UIDB\/04138\/2020","UIDP\/04138\/2020","2021.06598.BD","951996","022161","EAPA_0032\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Sphaerococcenol A is a cytotoxic bromoditerpene biosynthesized by the red alga Sphaerococcus coronopifolius. A series of its analogues (1\u20136) was designed and semi-synthesized using thiol-Michael additions and enone reduction, and the structures of these analogues were characterized by spectroscopic methods. Cytotoxic analyses (1\u2013100 \u00b5M; 24 h) were accomplished on A549, DU-145, and MCF-7 cells. The six novel sphaerococcenol A analogues displayed an IC50 range between 14.31 and 70.11 \u00b5M on A549, DU-145, and MCF-7 malignant cells. Compound 1, resulting from the chemical addition of 4-methoxybenzenethiol, exhibited the smallest IC50 values on the A549 (18.70 \u00b5M) and DU-145 (15.82 \u00b5M) cell lines, and compound 3, resulting from the chemical addition of propanethiol, exhibited the smallest IC50 value (14.31 \u00b5M) on MCF-7 cells. The highest IC50 values were exhibited by compound 4, suggesting that the chemical addition of benzylthiol led to a loss of cytotoxic activity. The remaining chemical modifications were not able to potentiate the cytotoxicity of the original compounds. Regarding A549 cell viability, analogue 1 exhibited a marked effect on mitochondrial function, which was accompanied by an increase in ROS levels, Caspase-3 activation, and DNA fragmentation and condensation. This study opens new avenues for research by exploring sphaerococcenol A as a scaffold for the synthesis of novel bioactive molecules.<\/jats:p>","DOI":"10.3390\/md22090408","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T08:36:08Z","timestamp":1725525368000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sphaerococcenol A Derivatives: Design, Synthesis, and Cytotoxicity"],"prefix":"10.3390","volume":"22","author":[{"given":"D\u00eddia","family":"Sousa","sequence":"first","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1072-0709","authenticated-orcid":false,"given":"Milene A. G.","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-1699","authenticated-orcid":false,"given":"Joana","family":"Silva","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]},{"given":"M\u00f3nica","family":"Pingo","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]},{"given":"Alice","family":"Martins","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-5948","authenticated-orcid":false,"given":"Carlos A. M.","family":"Afonso","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Rui","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4514-9154","authenticated-orcid":false,"given":"Filipa","family":"Siopa","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-2127","authenticated-orcid":false,"given":"Celso","family":"Alves","sequence":"additional","affiliation":[{"name":"MARE\u2014Marine and Environmental Sciences Centre\/ARNET\u2014Aquatic Research Network, ESTM, Polit\u00e9cnico de Leiria, 2520-614 Peniche, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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