{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:59:36Z","timestamp":1775869176036,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Grant PI21\/02045"],"award-info":[{"award-number":["Grant PI21\/02045"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Cancer caused 9.9 million deaths in 2020, and natural products and\/or their structural analogs represent the greatest number of approved small\u2010molecules antitumor agents. Benzopyran and quinoline heterocycles have demonstrated cytotoxic activity against different cancer cell lines. Due to its high therapeutic potential, we report the synthesis of 2\u2010propanamide\u2010 and 2\u2010propanamine\u2010dihydrobenzopyrans bearing different amine moieties in the side chain, as well as the 7\u2010carbon prenylated derivatives (analogous to natural polyalthidin). Next, we synthesized the 2\u2010substituted and 2,3\u2010disubstituted quinolines as benzopyran analogs. We evaluated the cytotoxic activity of all nitrogenated derivatives against human cancer cell lines, including A549 (lung cancer), A2058 (melanoma), HepG2 (hepatocellular carcinoma), MCF\u20107 (breast cancer), and Mia PaCa\u20102 (pancreas cancer) by the MTT assay. Structure\u2013activity relationship analysis revealed: (i) the benzopyran core was twofold more cytotoxic than quinoline analogs and reached ED\n                    <jats:sub>50<\/jats:sub>\n                    values in the low micromolar range (ED\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&lt;\u200910\u2009\u03bcM) against A2058, HepG2, and MCF\u20107; (ii) benzopyran amides showed higher cytotoxicity than benzopyran amines against MCF\u20107, and afforded better results for studied lines except for Mia PaCa\u20102; and (iii) the amine moiety introduced at 2\u2010position played a key role for activity; (iv) benzyl and\n                    <jats:italic>p<\/jats:italic>\n                    \u2010fluorobenzyl substituents protecting phenol group at 6\u2010position afforded a similar cytotoxicity.\n                  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