Open AccessInducing apoptosis through upregulation of p53: structure–activity exploration of anthraquinone analogs
Author(s) -
Abiodun Anifowose,
Ayodeji A. Agbowuro,
Ravi Tripathi,
Lu Wen,
Chalet Tan,
Xiaoxiao Yang,
Binghe Wang
Publication year - 2020
Publication title -
medicinal chemistry research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.352
H-Index - 45
eISSN - 1554-8120
pISSN - 1054-2523
DOI - 10.1007/s00044-020-02563-y
Subject(s) - downregulation and upregulation , anthraquinone , chemistry , cytotoxicity , apoptosis , combinatorial chemistry , stereochemistry , biochemistry , microbiology and biotechnology , in vitro , organic chemistry , biology , gene
We previously reported a series of p53-elevating anthraquinone compounds with considerable cytotoxicity for acute lymphatic leukemia (ALL) cells. To further develop this class of compounds, we examined the effect of a few key structural features on the anticancer structure-activity relationship in ALL cells. The active analogs showed comparable cytotoxicity and upregulation of p53 but did not induce significant downregulation of MDM2 as seen with the lead compound AQ-101 , indicating the importance of the anthraquinone core scaffold for MDM2 regulation. The result from the current study not only contributes to the SAR framework of these anthraquinone derivatives but also opens up new chemical space for further optimization work.