Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells

R Shirai; H Takayama; A Nishikawa; Y Koiso; Y Hashimoto

doi:10.1016/s0960-894x(98)00344-8

Asymmetric synthesis of antimitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells

Bioorg Med Chem Lett. 1998 Aug 4;8(15):1997-2000. doi: 10.1016/s0960-894x(98)00344-8.

Authors

R Shirai¹, H Takayama, A Nishikawa, Y Koiso, Y Hashimoto

Affiliation

¹ Institute of Molecular and Cellular Biosciences (IMCB), University of Tokyo, Japan.

PMID: 9873473
DOI: 10.1016/s0960-894x(98)00344-8

Abstract

The (S,S)-enantiomer of combretadioxolane (3), designed as a chirally preorganized derivative of combretastatin A-4, exhibited quite strong tubulin polymerization-inhibitory activity (IC50: 4-6 microM). (S,S)-3 is 20 times more potent than vincristine as an in vitro growth inhibitor (in terms of GI50) of the multi-drug-resistant (MDR) cell line PC-12, which produces P-glycoprotein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Cell Division / drug effects
Dioxolanes / chemical synthesis*
Dioxolanes / pharmacology
Drug Resistance, Multiple*
PC12 Cells
Rats

Substances

Antineoplastic Agents
Dioxolanes
combretadioxolane