The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells |
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| Authors: | Ya-Hui Ding Hong-Xia Fan Jing Long Quan Zhang Yue Chen |
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| Institution: | College of Pharmacy, The State Key Laboratory of Elemento-Organic Chemistry, Synergetic Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China |
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| Abstract: | A series of guaianolide-type sesquiterpene lactones derivatives with arylation of α-methylene-γ-lactone moiety was synthesized using Heck reactions, and was evaluated for their activities against acute myelogenous leukemia (AML) cell line HL-60 and doxorubicin-resistant cell line HL-60/A. Although all compounds were significantly less active against HL-60 than the parent molecules, surprisingly, compounds 3a, 4c–4e, 5e, and 8d exhibited high potency against doxorubicin-resistant cell line HL-60/A (IC50 = 6.2–19 μM), and their activities against HL-60/A were comparable to that of their parent molecules. In view of their novel activities against HL-60/A, compound 5e with inhibitory activity against HL-60/A (IC50 = 6.2 ± 0.5 μM) was selected for study its preliminary mechanism. The result reveals that compound 5e can obviously induce apoptosis. |
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| Keywords: | Acute myelogenous leukemia Guaianolide-type sesquiterpene lactones Micheliolide Dehydrocostus lactone Synthesis |
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