253327-67-2Relevant academic research and scientific papers
A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility
Ma, Yun-Tao,Yang, Yanting,Cai, Pei,Sun, De-Yang,Sánchez-Murcia, Pedro A.,Zhang, Xiao-Ying,Jia, Wen-Qiang,Lei, Lei,Guo, Mengqi,Gago, Federico,Wang, Hongbo,Fang, Wei-Shuo
, p. 524 - 533 (2018)
A dual-purpose strategy aimed at enhancing the binding affinity for microtubules and improving the water solubility of docetaxel led to the design and synthesis of a series of C-2- and C-3′-modified analogues. Both aims were realized when the C-3′ phenyl group present in docetaxel was replaced with a propargyl alcohol. The resulting compound, 3f, was able to overcome drug resistance in cultured P-gp-overexpressing tumor cells and showed greater activity than docetaxel against drug-resistant A2780/AD ovarian cancer xenografts in mice. In addition, the considerably lower hydrophobicity of 3f relative to both docetaxel and paclitaxel led to better aqueous solubility. A molecular model of tubulin-bound 3f revealed novel hydrogen-bonding interactions between the propargyl alcohol and the polar environment provided by the side chains of Ser236, Glu27, and Arg320.
Conformationally restricted paclitaxel analogues: Macrocyclic mimics of the 'hydrophobic collapse' conformation
Boge, Thomas C.,Wu, Zhi-Jun,Himes, Richard H.,Vander Velde, David G.,Georg, Gunda I.
, p. 3047 - 3052 (2007/10/03)
Conformationally restricted macrocyclic analogues of paclitaxel were prepared, by connecting the 3'-phenyl group the 2-benzoate moiety with two-atom tethers to mimic the 'hydrophobic collapse' paclitaxel conformation. The analogues did not show activity in a tubulin assembly assay.
