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A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in vitro and some hybrid molecules showed an expected activity.

To establish the conformation of vitamin D compounds responsible for biological activity, a 1,25-dihydroxy-19-norvitamin D analogue 4possessing a 1-hydroxy group fixed in the axial orientation (-chair form) was synthesized. The starting compounds were bicyclic lactones 6, 7a, and 7b, derived from the quinic acid lactone, which were converted to the bicyclic ketone 13. Julia coupling of this compound with sulfone 15produced the 19-norvitamin D analogue 4, possessing an additional ring connecting the 3-oxygen and C-2, and the isomeric 3-hydroxy compound 5. In vitro, both analogues 4and 5exhibit reduced activity compared to the natural hormone 1, but the binding, differentiation, and transcriptional activities of analogue 5are markedly higher than that of 4constrained in the -chair conformation. Surprisingly, in vivotests in mice showed that the analogue 4significantly increases serum calcium at dose levels similar to 1,25-(OH)2D3. These seemingly discordant results are discussed. [ABSTRACT FROM AUTHOR]