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

  • Bioorg Med Chem Lett. 2015 Oct 15;25(20):4553-6. doi: 10.1016/j.bmcl.2015.08.064.
Qiao-Hong Chen  1 ,  Kevin Yu  2 ,  Xiaojie Zhang  2 ,  Guanglin Chen  2 ,  Andrew Hoover  2 ,  Francisco Leon  2 ,  Rubing Wang  2 ,  Nithya Subrahmanyam  2 ,  Ermias Addo Mekuria  3 ,  Liva Harinantenaina Rakotondraibe  3
Affiliations
  • 1. Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA. Electronic address: [email protected].
  • 2. Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
  • 3. College of Pharmacy/Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, 434 Parks Hall, 500 W 12th Avenue, Columbus, OH 43210, USA.
PMID: 26341135 DOI: 10.1016/j.bmcl.2015.08.064
Abstract

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.

Keywords
Cell proliferation; Chromone; Curcumin; Prostate cancer; Synergistic effect.