Abstract:
:To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Yu H,Hou Z,Tian Y,Mou Y,Guo Cdoi
10.1016/j.ejmech.2018.04.005subject
Has Abstractpub_date
2018-05-10 00:00:00pages
434-449eissn
0223-5234issn
1768-3254pii
S0223-5234(18)30332-5journal_volume
151pub_type
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