Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.

中文翻译：

---

Englerin A 的桥头堡修饰可降低 TRPC4 活性和静脉毒性，但不会降低细胞生长抑制。

对 englerin A 的桥头位置进行了修改，以探索该位点的变异对分子生物活性的影响，如 NCI 60 筛选所判断的那样，其中 englerin A 对肾癌细胞具有高效和选择性。用其他更大的取代基取代异丙基产生的化合物显示出与天然产物相当的优异选择性和效力。还评估了所选化合物对离子通道 TRPC4 的影响以及对小鼠的静脉毒性，与 englerin A 相比，这些化合物在两种测定中的效力均较低。