Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue

Luciano Barboni; Guido Giarlo; Massimo Ricciutelli; Roberto Ballini; Gunda I. Georg; David G. VanderVelde; Richard H. Himes; Minmin Wang; Ami Lakdawala; James P. Snyder

doi:10.1021/ol036204c

Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue

Luciano Barboni, Guido Giarlo, Massimo Ricciutelli, Roberto Ballini, Gunda I. Georg, David G. VanderVelde, Richard H. Himes, Minmin Wang, Ami Lakdawala, James P. Snyder

Medicinal Chemistry

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

30 Scopus citations

Abstract

(Equation presented) We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.

Original language	English (US)
Pages (from-to)	461-464
Number of pages	4
Journal	Organic Letters
Volume	6
Issue number	4
DOIs	https://doi.org/10.1021/ol036204c
State	Published - Feb 19 2004

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title = "Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue",

abstract = "(Equation presented) We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.",

author = "Luciano Barboni and Guido Giarlo and Massimo Ricciutelli and Roberto Ballini and Georg, {Gunda I.} and VanderVelde, {David G.} and Himes, {Richard H.} and Minmin Wang and Ami Lakdawala and Snyder, {James P.}",

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T1 - Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue

AU - Barboni, Luciano

AU - Giarlo, Guido

AU - Ricciutelli, Massimo

AU - Ballini, Roberto

AU - Georg, Gunda I.

AU - VanderVelde, David G.

AU - Himes, Richard H.

AU - Wang, Minmin

AU - Lakdawala, Ami

AU - Snyder, James P.

PY - 2004/2/19

Y1 - 2004/2/19

N2 - (Equation presented) We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.

AB - (Equation presented) We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.

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Synthesis, Modeling, and Anti-Tubulin Activity of a D-Seco Paclitaxel Analogue

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