{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T05:21:55Z","timestamp":1776489715360,"version":"3.51.2"},"reference-count":76,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Group of Marine Natural Products and Medicinal Chemistry\u2014CIIMAR","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Group of Marine Natural Products and Medicinal Chemistry\u2014CIIMAR","doi-asserted-by":"publisher","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Group of Marine Natural Products and Medicinal Chemistry\u2014CIIMAR","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"LAQV\/REQUIMTE","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"LAQV\/REQUIMTE","doi-asserted-by":"publisher","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"LAQV\/REQUIMTE","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT and ERDF","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}]},{"name":"FCT and ERDF","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}]},{"name":"FCT and ERDF","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>We previously reported that chalcone CM-M345 (1) and diarylpentanoid BP-C4 (2) induced p53-dependent growth inhibitory activity in human cancer cells. Herein, CM-M345 (1) and BP-C4 (2) analogues were designed and synthesized in order to obtain more potent and selective compounds. Compounds 16, 17, 19, 20, and 22\u201324 caused pronounced in vitro growth inhibitory activity in HCT116 cells (0.09 &lt; GI50 &lt; 3.10 \u03bcM). Chemical optimization of CM-M345 (1) led to the identification of compound 36 with increased selectivity for HCT116 cells expressing wild-type p53 compared to its p53-null isogenic derivative and low toxicity to non-tumor HFF-1 cells. The molecular modification of BP-C4 (2) resulted in the discovery of compound 16 with more pronounced antiproliferative activity and being selective for HCT116 cells with p53, as well as 17 with enhanced antiproliferative activity against HCT116 cells and low toxicity to non-tumor cells. Compound 16 behaved as an inhibitor of p53\u2013MDM2 interaction, and compound 17 was shown to induce apoptosis, associated with an increase in cleaved PARP and decreased levels of the anti-apoptotic protein Bcl-2. In silico studies allowed us to predict the druglikeness and ADMET properties for 16 and 17. Docking and molecular dynamics studies predicted that 16 could bind stably to the MDM2 binding pocket.<\/jats:p>","DOI":"10.3390\/ph16101354","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T03:53:00Z","timestamp":1695700380000},"page":"1354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure\u2013Activity Relationship Studies of Chalcones and Diarylpentanoids with Antitumor Activity: Potency and Selectivity Optimization"],"prefix":"10.3390","volume":"16","author":[{"given":"Joana","family":"Moreira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4050-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1125","authenticated-orcid":false,"given":"Joana B.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde (LAQV)\/REQUIMTE, Laborat\u00f3rio de Microbiologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Danilo","family":"Correia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira n\u00b0 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-2143","authenticated-orcid":false,"given":"Andreia","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4050-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4050-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde (LAQV)\/REQUIMTE, Laborat\u00f3rio de Microbiologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-1779","authenticated-orcid":false,"given":"Honorina","family":"Cidade","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4050-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liebl, M.C., and Hofmann, T.G. (2021). The role of p53 signaling in colorectal cancer. 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