Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives

Ruiwu Liu, Dali Yin, Donghui Wang, Chun Li, Jiyu Guo, Xiaotian Liang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)910-918
Number of pages9
JournalYaoxue Xuebao
Volume33
Issue number12
StatePublished - Dec 1998
Externally publishedYes

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Structure-Activity Relationship
Paclitaxel
Benzoates
Microtubules
Esters
Valerates
Taxoids
Antineoplastic Agents
Pharmacology
Cell Line

Keywords

  • Antitumor activity
  • Microtubule assembly assay
  • Novel 14β-side chain taxol derivative
  • Structure-activity relationships

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Liu, R., Yin, D., Wang, D., Li, C., Guo, J., & Liang, X. (1998). Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives. Yaoxue Xuebao, 33(12), 910-918.

Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives. / Liu, Ruiwu; Yin, Dali; Wang, Donghui; Li, Chun; Guo, Jiyu; Liang, Xiaotian.

In: Yaoxue Xuebao, Vol. 33, No. 12, 12.1998, p. 910-918.

Research output: Contribution to journalArticle

Liu, R, Yin, D, Wang, D, Li, C, Guo, J & Liang, X 1998, 'Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives', Yaoxue Xuebao, vol. 33, no. 12, pp. 910-918.
Liu, Ruiwu ; Yin, Dali ; Wang, Donghui ; Li, Chun ; Guo, Jiyu ; Liang, Xiaotian. / Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives. In: Yaoxue Xuebao. 1998 ; Vol. 33, No. 12. pp. 910-918.
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