1.Discovery and bioassay of disubstituted β-elemene-NO donor conjugates: synergistic enhancement in the treatment of leukemia.
Junlong ZHU ; Xiaoying JIANG ; Xinyu LUO ; Yuan GAO ; Rui ZHAO ; Junjie LI ; Hong CAI ; Xiawen DANG ; Xiangyang YE ; Renren BAI ; Tian XIE
Chinese Journal of Natural Medicines (English Ed.) 2023;21(12):916-926
Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans
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Mice
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Animals
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Cell Line, Tumor
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Nitric Oxide Donors/pharmacology*
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Sesquiterpenes/pharmacology*
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Leukemia/drug therapy*
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Biological Assay
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Cell Proliferation