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 language | English (US) |
|---|---|
| Pages (from-to) | 910-918 |
| Number of pages | 9 |
| Journal | Yaoxue Xuebao |
| Volume | 33 |
| Issue number | 12 |
| State | Published - Dec 1998 |
| Externally published | Yes |
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Keywords
- Antitumor activity
- Microtubule assembly assay
- Novel 14β-side chain taxol derivative
- Structure-activity relationships
ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Synthesis and structure-activity relationships of novel 14β-side chain taxol derivatives
AU - Liu, Ruiwu
AU - Yin, Dali
AU - Wang, Donghui
AU - Li, Chun
AU - Guo, Jiyu
AU - Liang, Xiaotian
PY - 1998/12
Y1 - 1998/12
N2 - 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.
AB - 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.
KW - Antitumor activity
KW - Microtubule assembly assay
KW - Novel 14β-side chain taxol derivative
KW - Structure-activity relationships
UR - http://www.scopus.com/inward/record.url?scp=0032226203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032226203&partnerID=8YFLogxK
M3 - Article
C2 - 12016856
AN - SCOPUS:0032226203
VL - 33
SP - 910
EP - 918
JO - Yao xue xue bao = Acta pharmaceutica Sinica
JF - Yao xue xue bao = Acta pharmaceutica Sinica
SN - 0513-4870
IS - 12
ER -