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

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31 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.\}",

year = "2004",

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doi = "10.1021/ol036204c",

language = "English (US)",

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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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U2 - 10.1021/ol036204c

DO - 10.1021/ol036204c

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AN - SCOPUS:10744225655

SN - 1523-7060

VL - 6

SP - 461

EP - 464

JO - Organic Letters

JF - Organic Letters

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ER -

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

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