Bioorganic & Medicinal Chemistry Letters, 2015, 25(20):4553-4556.

A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation

Qiao-Hong Chen, Kevin Yu, Xiaojie Zhang, et al

Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA; College of Pharmacy/Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, 434 Parks Hall, 500 W 12th Avenue, Columbus, OH 43210, USA

Inspired by the synergistic effects of dietary natural products with different scaffolds on the inhibition of cancer cell proliferation, incorporation of central (1E,4E)-1,4-penta-dien-3-one linker (an optimal substitute for the central metabolically unstable diketone linker of curcumin), 1-alkyl-1H-imidazol-2-yl (a promising bioisostere of terminal aryl group in curcumin), and chromone (the common pharmacophore in genistein and quercetin) into one chemical entity resulted in ten new hybrid molecules, 3-((1E,4E)-5-(1-alkyl-1H-imidazol-2-yl)-3-oxopenta-1,4-dien-1-yl)-4H-chromen-4-ones. They were synthesized through a three-step transformation using acid-catalyzed aldol condensation as key step. The WST-1 cell proliferation assay showed that they have greater anti-proliferative potency than curcumin, quercetin, and genistein on both androgen-dependent and androgen-independent human prostate cancer cells.

英国《生物有机和药物化学快讯》，2015年10月

灵感来源于姜黄色素和金雀异黄素协同作用的一类新型混合抗癌试剂：设计、 合成及抗增殖作用的评估

陈乔红，于凯文，张晓杰，等

美国加州州立大学化学系； 俄亥俄州立大学药学院药物化学和生药学系

受到膳食天然产物与不同支架对抑制癌细胞增殖的协同作用的启发，引入中枢（1E，4E）-1,4-五烯-3-酮链（一种中枢代谢不稳定的最佳替代物 姜黄素的二酮链），1-烷基-1H-咪唑-2-基（在生物电子显微镜下有希望的姜黄素末端芳基）和色酮（金雀异黄素和槲皮素中的共同药效基团）转化为一种化学实体，生成十种新的杂交分子 ，3 - （（1E，4E）-5-（1-烷基-1H-咪唑-2-基）-3-氧代五氢-1,4-二烯-1-基）-4H-色烯-4-酮。 通过三步转化合成它们，并且使用酸催化的醛醇缩合作为关键步骤。 WST-1细胞增殖测定显示，它们在雄激素依赖性和雄激素依赖性的前列腺癌细胞上具有比姜黄素，槲皮素和金雀异黄素更强的抗增殖能力。