Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of camptothecin derivatives and HDAC inhibitors. To exploit this synergy in a single active compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the psammaplin A scaffold showed a broad spectrum of antiproliferative activity, with IC₅₀ values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability.

最近的研究表明，由喜树碱衍生物和HDAC抑制剂组成的联合疗法具有增强的抗癌作用。为了在单一活性化合物中发挥这种协同作用，我们设计了同时靶向拓扑异构酶I和HDAC的新型双作用多价分子。特别地，包含喜树碱和psammaplin A支架的所选化合物显示出广谱的抗增殖活性，IC ₅₀值在纳摩尔范围内。初步的体内结果表明对CD-1裸鼠原位异种移植的人间皮瘤原代细胞MM473有很强的抗肿瘤活性，并且具有很高的耐受性。