2. Academic Validation
  3. The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells

The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells

  • Bioorg Med Chem Lett. 2013 Nov 15;23(22):6087-92. doi: 10.1016/j.bmcl.2013.09.028.
Ya-Hui Ding 1,  Hong-Xia Fan,  Jing Long,  Quan Zhang,  Yue Chen
Affiliations

Affiliation

  • 1 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.
PMID: 24095093 DOI: 10.1016/j.bmcl.2013.09.028
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.

Keywords

Acute myelogenous leukemia; Dehydrocostus lactone; Guaianolide-type sesquiterpene lactones; Micheliolide; Synthesis.

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