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.
- 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.
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.