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.
Bioorganic & medicinal chemistry letters. 2015 Aug 24 [Epub ahead of print]
Qiao-Hong Chen, Kevin Yu, Xiaojie Zhang, Guanglin Chen, Andrew Hoover, Francisco Leon, Rubing Wang, Nithya Subrahmanyam, Ermias Addo Mekuria, Liva Harinantenaina Rakotondraibe
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., College of Pharmacy/Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, 434 Parks Hall, 500 W 12th Avenue, Columbus, OH 43210, USA.