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Drug repurposing: Discovery of troxipide analogs as potent antitumor agents.
- Source :
-
European Journal of Medicinal Chemistry . Sep2020, Vol. 202, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- Drug repurposing plays a vital role in the discovery of undescribed bioactivities in clinical drugs. Based on drug repurposing strategy, we for the first time reported a novel series of troxipide analogs and then evaluated their antiproliferative activity against MCF-7, PC3, MGC-803, and PC9 cancer cell lines and WPMY-1, most of which showed obvious selectivity toward PC-3 over the other three cancer cell lines and WPMY-1. Compound 5q , especially, could effectively inhibit PC3 with an IC 50 value of 0.91 μM, which exhibited around 53-fold selectivity toward WPMY-1. Data indicated that 5q effectively inhibited the colony formation, suppressed the cell migration, and induced G1/S phase arrest in PC3 cells. Also, compound 5q induced cell apoptosis by activating the two apoptotic signaling pathways in PC3 cells: death receptor-mediated extrinsic pathway and mitochondria-mediated intrinsic pathway. Compound 5q up-regulated the expression of both pro-apoptotic Bax and P53, while down-regulated anti-apoptotic Bcl-2 expression. Besides, compound 5q significantly increased the expression of cleaved caspase 3/9 and cleaved PARP. Therefore, the successful discovery of compound 5q may further validate the feasibility of this theory, which will encourage researchers to reveal undescribed bioactivities in traditional drugs. Image 1 • A novel series of troxipide analogs were designed using drug repurposing strategy. • 5q effectively inhibited PC3 (IC 50 = 0.91 μM), being around 53-fold selectivity toward WPMY-1. • 5q effectively inhibited the colony formation, suppressed the cell migration, and induced G1/S phase arrest in PC3. • 5q induced apoptosis by activating death receptor-mediated extrinsic and mitochondria-mediated intrinsic pathways in PC3. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 202
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 145071059
- Full Text :
- https://doi.org/10.1016/j.ejmech.2020.112471