Antimicrotubular and cytotoxic activity of geiparvarin analogues, alone and in combination with paclitaxel

Geiparvarin is an antiproliferative compound isolated from the leaves of Ge ijera parviflora, and may represent a new drug which targets tubulin. To be tter explore the potential use of this agent, we investigated the antimicro tubular and cytotoxic effects of new synthetic aromatic derivatives of geip arvarin. These drugs inhibited polymerization of microtubular protein, part icularly when the assembly was induced by paclitaxel. The microtubular netw ork organization of fibroblasts was altered more effectively by some drugs. Normal microtubule architecture completely disappeared when the cells were treated simultaneously with drugs and paclitaxel: microtubules depolymeriz ed or were reorganized into bundles, in a similar but more disarrayed fashi on than that observed after treatment with paclitaxel alone. Cytotoxicity s tudies showed a dose-dependent effect, whereas combined administration of d rugs and paclitaxel increased cytotoxicity, more effectively in paclitaxel versus derivatives administration alone. Copyright (C) 2001 John Wiley & So ns, Ltd.