Preparation and biological activity of taxol acetates

Wilfredo Mellado; Neal F. Magri; David G.I. Kingston; Renee Garcia-Arenas; George A. Orr; Susan Band Horwitz

doi:10.1016/0006-291X(84)91557-2

Preparation and biological activity of taxol acetates

Wilfredo Mellado, Neal F. Magri, David G.I. Kingston, Renee Garcia-Arenas, George A. Orr, Susan Band Horwitz

Research output: Contribution to journal › Article › peer-review

97 Scopus citations

Abstract

Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured in vivo by cytotoxicity toward the macrophage-like cell line J774.2, and in vitro by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of in vitro activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on in vitro microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for in vitro activity and this position is available for structural modifications.

Original language	English (US)
Pages (from-to)	329-336
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	124
Issue number	2
DOIs	https://doi.org/10.1016/0006-291X(84)91557-2
State	Published - Oct 30 1984
Externally published	Yes

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/0006-291X(84)91557-2

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@article{179f19dbdf6c4a86932383e6b4a08d33,

title = "Preparation and biological activity of taxol acetates",

abstract = "Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured in vivo by cytotoxicity toward the macrophage-like cell line J774.2, and in vitro by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of in vitro activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on in vitro microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for in vitro activity and this position is available for structural modifications.",

author = "Wilfredo Mellado and Magri, {Neal F.} and Kingston, {David G.I.} and Renee Garcia-Arenas and Orr, {George A.} and Horwitz, {Susan Band}",

note = "Funding Information: at the C-2' position such as the addition of charged to enhance solubility. It is reasonable to expect that position would be removed --in vivo and a biologically ACKNOWLEDGEMENTS: WM is a Merck Predoctoral Fellow. DGIK acknowledges support of the American Cancer Society (grant CH-268) and a gift of taxol from Dr. F. Boettner (Polysciences, Inc.) through Dr. M. Suffness (N.C.I.). SBH acknowledges support of USPHS grants CA 17514 and GM 29042 and American Cancer Society grant CH-86. The authors thank Dr.C.F. Brewer for help with the NMR studies.",

year = "1984",

month = oct,

day = "30",

doi = "10.1016/0006-291X(84)91557-2",

language = "English (US)",

volume = "124",

pages = "329--336",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Preparation and biological activity of taxol acetates

AU - Mellado, Wilfredo

AU - Magri, Neal F.

AU - Kingston, David G.I.

AU - Garcia-Arenas, Renee

AU - Orr, George A.

AU - Horwitz, Susan Band

N1 - Funding Information: at the C-2' position such as the addition of charged to enhance solubility. It is reasonable to expect that position would be removed --in vivo and a biologically ACKNOWLEDGEMENTS: WM is a Merck Predoctoral Fellow. DGIK acknowledges support of the American Cancer Society (grant CH-268) and a gift of taxol from Dr. F. Boettner (Polysciences, Inc.) through Dr. M. Suffness (N.C.I.). SBH acknowledges support of USPHS grants CA 17514 and GM 29042 and American Cancer Society grant CH-86. The authors thank Dr.C.F. Brewer for help with the NMR studies.

PY - 1984/10/30

Y1 - 1984/10/30

N2 - Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured in vivo by cytotoxicity toward the macrophage-like cell line J774.2, and in vitro by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of in vitro activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on in vitro microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for in vitro activity and this position is available for structural modifications.

AB - Synthesis and biological activity of 2′-acetyltaxol and 7-acetyltaxol are reported. Activity is measured in vivo by cytotoxicity toward the macrophage-like cell line J774.2, and in vitro by promotion of microtubule assembly in the absence of exogenous GTP. Addition of an acetyl moiety at C-2′ results in loss of in vitro activity but not cytotoxicity. The properties of 7-acetyltaxol are similar to those of taxol in its effects on cell replication and on in vitro microtubule polymerization. Therefore a free hydroxyl group at C-7 is not required for in vitro activity and this position is available for structural modifications.

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VL - 124

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EP - 336

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -

Preparation and biological activity of taxol acetates

Abstract

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