The unique chemical and physical properties of ferrocene have made it an interesting pharmacophore for drug design and conjugation of this organometallic system with biologically active compounds has proven a successful approach in the development of new derivatives with enhanced activity. As striking examples, ferrocifen and ferroquine, that are the organometallic analogues of antiestrogen tamoxifen and the antimalarial chloroquine, are at the clinical stage for their use in therapy and their activity is beneficially related with the redox properties of the ferrocene unit.1 We have recently reported the preparation of compound 1 as the first curcumin-related biphenyl and found it more effective in inhibiting malignant melanoma and neuroblastoma cells growth when compared to curcumin itself.2 Inhibition of the aggregation process of ?alpha-synuclein was also shown for biphenyls 1 and 2, the latter the dimeric analogue of dehydrozingerone 7. With the aim to explore the effect of a ferrocenyl unit (Fc) in a set of dehydrozingerone-related structures, ferrocenyl conjugates of biphenyls 1-3 as well as of the corresponding monomers were synthesized via straightforward methods and their electrochemical potential and cytotoxic activity in PC12 cells were evaluated in comparison with data of the corresponding compounds lacking in the organometallic moiety. From the obtained results some positive influence on the stability toward oxidation and biological activity due to the presence of the ferrocene unit(s) in molecular structure could be evidenced.
Synthesis of new ferrocene-dehydrozingerone conjugates and evaluation of their biological activity
Patti A;Pedotti S;Barberis A;Fabbri D;Dettori M A;Delogu G
2014
Abstract
The unique chemical and physical properties of ferrocene have made it an interesting pharmacophore for drug design and conjugation of this organometallic system with biologically active compounds has proven a successful approach in the development of new derivatives with enhanced activity. As striking examples, ferrocifen and ferroquine, that are the organometallic analogues of antiestrogen tamoxifen and the antimalarial chloroquine, are at the clinical stage for their use in therapy and their activity is beneficially related with the redox properties of the ferrocene unit.1 We have recently reported the preparation of compound 1 as the first curcumin-related biphenyl and found it more effective in inhibiting malignant melanoma and neuroblastoma cells growth when compared to curcumin itself.2 Inhibition of the aggregation process of ?alpha-synuclein was also shown for biphenyls 1 and 2, the latter the dimeric analogue of dehydrozingerone 7. With the aim to explore the effect of a ferrocenyl unit (Fc) in a set of dehydrozingerone-related structures, ferrocenyl conjugates of biphenyls 1-3 as well as of the corresponding monomers were synthesized via straightforward methods and their electrochemical potential and cytotoxic activity in PC12 cells were evaluated in comparison with data of the corresponding compounds lacking in the organometallic moiety. From the obtained results some positive influence on the stability toward oxidation and biological activity due to the presence of the ferrocene unit(s) in molecular structure could be evidenced.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
