Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives

Ranganathan Balasubramanian; Bhooma Raghavan; Jaeson C. Steele; Dan L. Sackett; Robert A. Fecik

doi:10.1016/j.bmcl.2008.03.046

Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives

Ranganathan Balasubramanian, Bhooma Raghavan, Jaeson C. Steele, Dan L. Sackett, Robert A. Fecik

Medicinal Chemistry

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

32 Scopus citations

Abstract

A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC₅₀ values similar to combretastatin A4 and the hemiasterlin analog HTI-286.

Original language	English (US)
Pages (from-to)	2996-2999
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2008.03.046
State	Published - May 1 2008

Bibliographical note

Funding Information:
This work was generously supported by the American Cancer Society, Grant RSG-05-105-01-CDD (to R.A.F.), and was supported in part by intramural funds from the National Institute of Child Health and Human Development, NIH. Funding for NMR instrumentation in the Department of Biochemistry, Molecular Biology, and Biophysics was provided by the University of Minnesota Medical School, NSF (BIR-961477), and the Minnesota Medical Foundation.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

Anticancer agents
Cytotoxicity
Natural products
Tubulin
Tubulysin

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2008.03.046

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title = "Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives",

abstract = "A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC50 values similar to combretastatin A4 and the hemiasterlin analog HTI-286.",

keywords = "Anticancer agents, Cytotoxicity, Natural products, Tubulin, Tubulysin",

author = "Ranganathan Balasubramanian and Bhooma Raghavan and Steele, {Jaeson C.} and Sackett, {Dan L.} and Fecik, {Robert A.}",

note = "Funding Information: This work was generously supported by the American Cancer Society, Grant RSG-05-105-01-CDD (to R.A.F.), and was supported in part by intramural funds from the National Institute of Child Health and Human Development, NIH. Funding for NMR instrumentation in the Department of Biochemistry, Molecular Biology, and Biophysics was provided by the University of Minnesota Medical School, NSF (BIR-961477), and the Minnesota Medical Foundation. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

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AU - Balasubramanian, Ranganathan

AU - Raghavan, Bhooma

AU - Steele, Jaeson C.

AU - Sackett, Dan L.

AU - Fecik, Robert A.

N1 - Funding Information: This work was generously supported by the American Cancer Society, Grant RSG-05-105-01-CDD (to R.A.F.), and was supported in part by intramural funds from the National Institute of Child Health and Human Development, NIH. Funding for NMR instrumentation in the Department of Biochemistry, Molecular Biology, and Biophysics was provided by the University of Minnesota Medical School, NSF (BIR-961477), and the Minnesota Medical Foundation. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC50 values similar to combretastatin A4 and the hemiasterlin analog HTI-286.

AB - A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC50 values similar to combretastatin A4 and the hemiasterlin analog HTI-286.

KW - Anticancer agents

KW - Cytotoxicity

KW - Natural products

KW - Tubulin

KW - Tubulysin

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IS - 9

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Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives

Abstract

Bibliographical note

Keywords

UN SDGs

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