Maccari Laura, Manetti Fabrizio, Corelli Federico, Botta Maurizio
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Aldo Moro, I-53100 Siena, Italy.
Farmaco. 2003 Sep;58(9):659-68. doi: 10.1016/s0014-827x(03)00099-5.
The antimitotic agent paclitaxel continues to play an important role in the cancer chemotherapy. However, its inefficacy on certain resistant cells and toxic side effects have led to the search of new taxanes with improved biological activity. By means of a pseudoreceptor modeling approach, we have developed a binding site model for a series of taxanes. It is the first 3D QSAR model derived from the experimentally determined tubulin structure obtained by electron crystallography studies. The model is able to correlate quantitatively the structural properties of the studied compounds with their biological data.
抗有丝分裂剂紫杉醇在癌症化疗中持续发挥重要作用。然而，其对某些耐药细胞的无效性以及毒副作用促使人们寻找具有更好生物活性的新型紫杉烷类化合物。通过一种虚拟受体建模方法，我们已经为一系列紫杉烷类化合物开发了一个结合位点模型。这是首个基于电子晶体学研究获得的实验确定的微管蛋白结构推导出来的三维定量构效关系（3D QSAR）模型。该模型能够将所研究化合物的结构性质与其生物学数据进行定量关联。
