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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Novel combretastatin analogues endowed with antitumor activity.

We studied the anticancer activity of a series of new combretastatin derivatives with B-ring modifications. The structure-activity relationship (SAR) information confirmed the importance of cis-stereochemistry and of a phenolic moiety in B-ring. We selected the benzo[b]thiophene and benzofuran combretastatin analogues 11 (ST2151) and 13 (ST2179) and their phosphate prodrugs (29 and 30) for their high antitumor activity in in vitro and in vivo models. Cell exposure to IC50 of 11, 13, and CA-4 led to the arrest of various cell types in the G2/M phase of the cell cycle and induction of apoptosis. Mainly, 11 and 13 induced the formation of multinucleated cells with abnormal chromatin distribution, with only a minimal effect on the microtubule organization, with respect to CA-4. Interestingly, both the pharmacokinetic profile of 29 and its in vivo antitumor effect and those of 30, active even after oral administration, suggest additional pharmacological differences between these compounds and CA-4P.[1]

References

  1. Novel combretastatin analogues endowed with antitumor activity. Simoni, D., Romagnoli, R., Baruchello, R., Rondanin, R., Rizzi, M., Pavani, M.G., Alloatti, D., Giannini, G., Marcellini, M., Riccioni, T., Castorina, M., Guglielmi, M.B., Bucci, F., Carminati, P., Pisano, C. J. Med. Chem. (2006) [Pubmed]
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