biostudies-literatureBozsity NNational Research, Development and Innovation OfficeNational Research, Development, and Innovation Office NKFIHMinistry of Innovation and Technology of Hungary4274https://www.ebi.ac.uk/biostudies/studies/S-EPMC11050183biostudies-literatureUnknown25(8)Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide-alkyne cycloaddition reactions. The two <i>trans</i>-16-azido-3-(<i>O</i>-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-<i>O</i>-propargyl-D-secoestrone alcohol or oxime. The antiproliferative International journal of molecular sciencesSynthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity.PMC11050183K 143690TKP2021-EGA-32SNN 139323TKP2021-EGA-17Kele ZResch VParagi GZupko ISzabo JPalhazi BNagy VMinorics RMernyak EBozsity NfalseSynthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity.Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide-alkyne cycloaddition reactions. The two <i>trans</i>-16-azido-3-(<i>O</i>-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-<i>O</i>-propargyl-D-secoestrone alcohol or oxime. The antiproliferative 2024-01-01T00:00:00Z2024 Apr2026-05-20T03:15:23.842Z2026-05-20T03:07:41.454ZS-EPMC110501833867386010.3390/ijms25084274