1. A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation
- Author
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Rubing Wang, Liva Harinantenaina Rakotondraibe, Qiao-Hong Chen, Andrew Hoover, Guanglin Chen, Kevin Yu, Francisco Leon, Xiaojie Zhang, Ermias Addo Mekuria, and Nithya Subrahmanyam
- Subjects
Curcumin ,Clinical Biochemistry ,Pharmaceutical Science ,Genistein ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Structure–activity relationship ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Drug Synergism ,chemistry ,Drug Design ,Chromone ,Cancer cell ,Molecular Medicine ,Bioisostere ,Drug Screening Assays, Antitumor ,Pharmacophore ,Linker - 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.
- Published
- 2015