Poly (ADP-ribose) polymerase (PARP) inhibitors have achieved great success in clinical application, especially for the prolonged survival of cisplatin-sensitive ovarian cancer patients. However, there are still many patients who do not respond to PARP inhibitors. Novel PARP inhibitors with higher activity are urgently needed. Herein we report a series of compounds by molecular hybridization PARP-1 inhibitor Olaparib (Ola) with HSP90 inhibitor C0817 (one curcumin derivative). All synthesized compounds were evaluated for their antiproliferative activity in vitro, and some were further assessed for their inhibitory activities of the PARP enzyme and HSP90 affinity. Our results indicated that compound 4 could bind to HSP90 and cause static quenching, indicating that compound 4 was able to bind to HSP90, moreover, downstream molecular breast cancer 1 (BRAC-1) was reduced. In conclusion, dual target inhibitors of PARP and HSP90 exhibited stronger selective cytotoxicities against cancer.

聚（ADP-核糖）聚合酶（PARP）抑制剂在临床应用中取得了巨大成功，尤其是对于顺铂敏感型卵巢癌患者的延长生存期。但是，仍然有许多患者对PARP抑制剂无反应。迫切需要具有更高活性的新型PARP抑制剂。本文中，我们通过分子杂交PARP-1抑制剂Olaparib（Ola）与HSP90抑制剂C0817（一种姜黄素衍生物）报告了一系列化合物。评估了所有合成的化合物的体外抗增殖活性，并进一步评估了其对PARP酶的抑制活性和HSP90亲和力。我们的结果表明，化合物4可以与HSP90结合并引起静态淬灭，这表明化合物4能够与HSP90结合，下游分子乳腺癌1（BRAC-1）减少。总之，PARP和HSP90的双重靶标抑制剂对癌症表现出更强的选择性细胞毒性。