TY - JOUR
T1 - Identification and biological activities of new taccalonolide microtubule stabilizers
AU - Peng, Jiangnan
AU - Risinger, April L.
AU - Fest, Gary A.
AU - Jackson, Evelyn M.
AU - Helms, Gregory
AU - Polin, Lisa A.
AU - Mooberry, Susan L.
PY - 2011/9/8
Y1 - 2011/9/8
N2 - The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods. The biological activities of the new taccalonolides, as well as taccalonolides A, B, E, N, R, and T, were evaluated. All nine taccalonolides display microtubule stabilizing activity, but profound differences in antiproliferative potencies were noted, with IC50 values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 μM). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure-activity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.
AB - The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods. The biological activities of the new taccalonolides, as well as taccalonolides A, B, E, N, R, and T, were evaluated. All nine taccalonolides display microtubule stabilizing activity, but profound differences in antiproliferative potencies were noted, with IC50 values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 μM). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure-activity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.
UR - http://www.scopus.com/inward/record.url?scp=80052383462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052383462&partnerID=8YFLogxK
U2 - 10.1021/jm200757g
DO - 10.1021/jm200757g
M3 - Article
C2 - 21800839
AN - SCOPUS:80052383462
SN - 0022-2623
VL - 54
SP - 6117
EP - 6124
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 17
ER -