A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities.
Li P-K., Pandit B., Sackett DL., Hu Z., Zink J., Zhi J., Freeman D., Robey RW., Werbovetz K., Lewis A., Li C.
We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent.