Discovery of Dolutegravir Derivative against Liver Cancer via Inducing Autophagy and DNA Damage
We introduced a terminal alkyne into the core structure of dolutegravir, resulting in the synthesis of 34 novel dolutegravir-1,2,3-triazole compounds through click chemistry. These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. N...
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Published in | Molecules (Basel, Switzerland) Vol. 29; no. 8; p. 1779 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
01.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | We introduced a terminal alkyne into the core structure of dolutegravir, resulting in the synthesis of 34 novel dolutegravir-1,2,3-triazole compounds through click chemistry. These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. Notably, compounds
and
demonstrated exceptional efficacy, particularly against Huh7 cells, with IC
values of 2.64 and 5.42 μM. Additionally, both compounds induced apoptosis in Huh7 cells, suppressed tumor cell clone formation, and elevated reactive oxygen species (ROS) levels, further promoting tumor cell apoptosis. Furthermore, compounds
and
activated the LC3 signaling pathway, inducing autophagy, and triggered the γ-H2AX signaling pathway, resulting in DNA damage in tumor cells. Compound
exhibited low toxicity, highlighting its potential as a promising anti-tumor drug. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1420-3049 1420-3049 |
DOI: | 10.3390/molecules29081779 |