Plocabulin, a marine natural polyketide isolated from the sponge Lithoplocamia lithistoides, is a novel and potent microtubule-destabilizing agent. Guided by the reported binding mode, several new analogs of plocabulin have been designed through removing the right aliphatic chain and further modifying on the carbamate group and the enamide unit. The preliminary results indicate that the right aliphatic chain in plocabulin is allowed to remove with a little loss of activity, the carbamate group plays a role in the activity, and particularly, the enamide unit has an important effect on the activity. This new finding will aid the design of novel potent tubulin-binding agents based on plocabulin.

Plocabulin 是一种从海绵Lithoplocamia lithistoides 中分离出来的海洋天然聚酮化合物，是一种新型有效的微管去稳定剂。以报道的结合模式为指导，通过去除右脂肪链并进一步修饰氨基甲酸酯基团和烯酰胺单元，设计了几种新的plocabulin类似物。初步结果表明，plocabulin中的右脂肪链被去除，活性损失很小，氨基甲酸酯基团在活性中起作用，特别是烯酰胺单元对活性有重要影响。这一新发现将有助于设计基于 plocabulin 的新型强效微管蛋白结合剂。