3‐D QSAR Studies of Microtubule Stabilizing Antimitotic Agents Towards Six Cancer Cell Lines

Abstract

The antimitotic agent paclitaxel continues to play an important role in cancer chemotherapy. However, its inefficacy on certain resistant cells and toxic side effects had led to the search for new drugs with improved biological activity. Here the QSAR models for microtubule stabilizing anticancer agents were performed to correlate their physicochemical properties with biological activity. Single and multiple linear regression models for six cancer cell lines were obtained with R 2 ! 0.65 and q 2 pre ! 0.6. Molecular mechanics energy and log P of the molecules account for the activity of taxanes towards B16 melanoma and breast cancer cells, respectively. The lowest unoccupied molecular orbitals and the number of nitrogen atoms in the structure account for the biological activity of epothilone derivatives and rest of the drugs towards ovarian cells. The relation between the structural properties of microtubule stabilizing antimitotic compounds and their activities on different cell lines are investigated in this paper.

Understanding Tubulin/Microtubule−Taxane Interactions: A Quantitative Structure–Activity Relationship Study

“…Various groups of compounds that interfere with the cell cycle have attracted major interest in the cancer research field because they inhibit the proliferation of cancer cells. These types of compounds (antimitotic) target the microtubules of the cells and generally fall into three distinct classes, which are based on their binding site on β-tubulin, namely the vincas, the colchicines, and the taxanes …”

Modeling resistance index of taxoids to MCF-7 cell lines using ANN together with electrotopological state descriptors

“…Since the last decade, there has been a lot QSAR-based research about taxoids [11][12][13][14][15] . Most of these studies made use of 3-D methods, such as the comparative molecular field analysis (COMFA) or the comparative molecular similarity indices analysis (COMSIA); another character of these researches is that the activity they adopted is IC 50 of taxoids to inhibit the disassembly of microtubule or growth of tumor cell lines instead of the RI of anti-MDR properties.…”