biostudies-literatureZhang QGreater Milwaukee FoundationNational Cancer InstituteNCI NIH HHSUniversity of Wisconsin-Milwaukee216-228https://www.ebi.ac.uk/biostudies/studies/S-EPMC12398329biostudies-literatureUnknown38(1)DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog <b>1</b> containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity. DNA ICLs were not observed with binaphthalene phenyl selenide <b>1</b> without UV irradiation, while ∼15% DNA ICL products were detected with UV irradiation, indicating a photoresponsive property of <b>1</b>. The trapping reactions with TEMPO and MeONH₂, respectively, suggested that free radicals and carbocations are involved in the DNA cross-linking process induced by the photoirradiation of <b>1</b>. TheChemical research in toxicologyA Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line.PMC123983291R15CA277656-01R15 CA277656Peng XAwoyera WOPonnamperumage TNFAli TOddiri RTFelli MCRasmussen ADLin ZFrick DNZhang QSetu NIfalseA Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line.DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog <b>1</b> containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity. DNA ICLs were not observed with binaphthalene phenyl selenide <b>1</b> without UV irradiation, while ∼15% DNA ICL products were detected with UV irradiation, indicating a photoresponsive property of <b>1</b>. The trapping reactions with TEMPO and MeONH₂, respectively, suggested that free radicals and carbocations are involved in the DNA cross-linking process induced by the photoirradiation of <b>1</b>. The2025-01-01T00:00:00Z2025 Jan2026-05-27T21:07:01.431Z2026-04-08T01:50:24.869ZS-EPMC123983293972105510.1021/acs.chemrestox.4c00499