Abstract：
In this work, a series of curcumin derivatives (1a-1h, 2a-2g, and 3a-3c) were synthesized for the suppression of castration-resistant prostate cancer cells. All synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and melting point. The in vitro cytotoxicity study shows that compounds 1a, 1e, 1f, 1h, 2g, 3a, and 3c display similar or enhanced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9, other synthesized compounds display reduced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9. Molecular docking simulation was performed to study the binding affinity and probable binding modes of the synthesized compounds with androgen receptor. The results show that all synthesized compounds exhibit higher cdocker interaction energies as compared to ASC-J9. Compounds 1h, 2g, and 3c not only show strong cytotoxicity against 22Rv1 and C4-2 cells but also exhibit high binding affinity with androgen receptor. In androgen receptor suppression study, compounds 1f and 2g show similar androgen receptor suppression effect as compared to ASC-J9 on C4-2 cells, compound 3c displays significantly enhanced AR suppression effect as compared to ASC-J9, 1f and 2g. Compounds 1a, 1e, 1f, 1h, 2g, 3a and 3c prepared in this work have significant potential for castration-resistant prostate cancer therapy.
摘要：
在这项工作中,一系列姜黄素衍生物(1a-1h，2a-2g,和3a-3c）被合成用于抑制去势抵抗的前列腺癌细胞。所有合成的化合物通过1HNMR表征，13CNMR,HRMS,和熔点。体外细胞毒性研究表明,化合物1a,1e,1f,1h,2g,3a,和3c显示与ASC-J9相比对22Rvl和C4-2细胞相似或增强的细胞毒性,其他合成的化合物显示与ASC-J9相比对22Rvl和C4-2细胞降低的细胞毒性。进行分子对接模拟以研究合成的化合物与雄激素受体的结合亲和力和可能的结合模式。结果表明，与ASC-J9相比，所有合成的化合物都表现出更高的cdocker相互作用能。化合物1h,2g,和3c不仅显示出对22Rv1和C4-2细胞的强细胞毒性,而且显示与雄激素受体的高结合亲和力。在雄激素受体抑制研究中，与ASC-J9相比，化合物1f和2g对C4-2细胞显示出相似的雄激素受体抑制作用，与ASC-J9、1f和2g相比,化合物3c显示出显著增强的AR抑制作用。化合物1a,1e,1f,1h,2g,在这项工作中制备的3a和3c具有用于去势抵抗前列腺癌治疗的巨大潜力。
