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Shvoong Home>Medicine & Health>SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIPS OF NOVEL 14β SIDE CHAIN TAXOL DERIVATIVES Summary

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SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIPS OF NOVEL 14β SIDE CHAIN TAXOL DERIVATIVES

Article Abstract by: TsingHua    

Original Author: ACTA PHARMACEUTICA SINICA
In order to develop new generation of taxol like anticancer agents with fewer side effects, improved activity, superior
pharmacological properties and broad antitumor spectrum, along with structure activity relationship study, a series of new taxol derivatives are to be synthesized starting from sinenxan A a biosynthetic taxane. Eight new 14β side chain taxol derivatives with 4 OH and 4 Ac were synthesized in 5 and 6 steps from semisynthetic taxoid intermediate 7, respectively. These included taxol derivatives modified at C 2 position with benzoate, m Cl benzoate, valerate and phenylacetate. All target compounds together with two other 14β side chain taxol derivatives were tested in a microtubule assembly assay, and in an in vitro cytotoxicity assay (KB, A2780, HCT 8 cell line). All compounds had no effect in the microtubule assembly assay at 10 μmol·L -1 . Most of them showed marginal activity in the in vitro cytotoxicity. The structure activity relationship was different from taxol derivatives. 2 Aliphatic ester displayed similar activity to 2 aromatic ester, which indicated that the aromatic group at C 2 position was not important for cytotoxicity. Comparing among themselves, 4 OH deravitives possessed stronger activity than 4 Ac.
Published: December 28, 1998
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