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These compounds exhibited remarkable inhibitory activities against two hepatocellular carcinoma cell lines, Huh7 and HepG2. Notably, compounds 5e and 5p demonstrated exceptional efficacy, particularly against Huh7 cells, with IC50 values of 2.64 and 5.42 \u03bcM. 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 5e and 5p activated the LC3 signaling pathway, inducing autophagy, and triggered the \u03b3-H2AX signaling pathway, resulting in DNA damage in tumor cells. Compound 5e exhibited low toxicity, highlighting its potential as a promising anti-tumor drug.<\/jats:p>","DOI":"10.3390\/molecules29081779","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T03:56:13Z","timestamp":1713153373000},"page":"1779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Discovery of Dolutegravir Derivative against Liver Cancer via Inducing Autophagy and DNA Damage"],"prefix":"10.3390","volume":"29","author":[{"given":"Xixi","family":"Hou","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longfei","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang 471003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huili","family":"Wang","sequence":"additional","affiliation":[{"name":"University of North Carolina Hospitals, 101 Manning Dr, Chapel Hill, Orange County, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Emergency, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxue","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1093\/jnci\/djm010","article-title":"AIDS-Related Cancer and Severity of Immunosuppression in Persons with AIDS","volume":"99","author":"Biggar","year":"2007","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1200\/JCO.2012.44.5486","article-title":"Incidence of HIV-Related Anal Cancer Remains Increased Despite Long-Term Combined Antiretroviral Treatment: Results from the French Hospital Database on HIV","volume":"30","author":"Piketty","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1038\/s41467-018-07006-2","article-title":"Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23213","DOI":"10.1074\/jbc.R100027200","article-title":"HIV integrase, a brief overview from chemistry to therapeutics","volume":"276","author":"Craigie","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1097\/QAD.0b013e328345ef5e","article-title":"Managing hepatitis B\/HIV co-infected: Adding entecavir to truvada (tenofovir disoproxil\/emtricitabine) experienced patients","volume":"25","author":"Ratcliffe","year":"2011","journal-title":"Aids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ward, A.S., Hsiung, C.H., Kesterson, D.G., Kamath, V.G., and McKee, E.E. (2022). Entecavir competitively inhibits deoxyguanosine and deoxyadenosine phosphorylation in isolated mitochondria and the perfused rat heart. J. Biol. Chem., 5.","DOI":"10.1016\/j.jbc.2022.101876"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/QAI.0b013e318198a88a","article-title":"Nonalcoholic fatty liver disease among HIV-infected persons","volume":"50","author":"Dilay","year":"2009","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jinf.2022.11.004","article-title":"Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus","volume":"86","author":"Santos","year":"2023","journal-title":"J. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1002\/lt.20534","article-title":"Pre-trasnplant survival is shorter in HIV-positive than HIV-negative with end-stage liver disease","volume":"11","author":"Ragni","year":"2005","journal-title":"Liver Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1365-2362.2010.02381.x","article-title":"Elevated TGF-\u03b21 levels might protect HCV\/HIV-coinfected patients from liver fibrosis","volume":"41","author":"Barreiro","year":"2011","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.clinre.2011.11.002","article-title":"Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir)","volume":"36","author":"Bourcier","year":"2012","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11904-019-00480-3","article-title":"Recent Advances in the Development of Integrase Inhibitors for HIV Treatment","volume":"17","author":"Trivedi","year":"2020","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1021\/jm400645w","article-title":"Carbamoyl pyridone HIV-1 integrase inhibitors 3. A diastereomeric approach to chiral nonracemic tricyclic ring systems and the discovery of dolutegravir (S\/GSK1349572) and (S\/GSK1265744)","volume":"56","author":"Johns","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/infdis\/jis750","article-title":"Safety and Efficacy of Dolutegravir in Treatment-Experienced Subjects with Raltegravir-Resistant HIV Type 1 Infection: 24-Week Results of the VIKING Study","volume":"207","author":"Eron","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.aay4919","article-title":"Structural basis of second-generation HIV integrase inhibitor action and viral resistance","volume":"367","author":"Cook","year":"2020","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, G.Y., Zhang, Z., Li, K., Liu, J., Li, B., Jin, Z., Liu, Y.H., and Tang, Y.Z. (2020). Design, synthesis and biological evaluation of novel pleuromutilin derivatives containing piperazine and 1,2,3-triazole linker. Bioorg. Chem., 105.","DOI":"10.1016\/j.bioorg.2020.104398"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111845","DOI":"10.1016\/j.ejmech.2019.111845","article-title":"Synthesis, antiproliferative activity and DNA\/RNA-binding properties of mono- and bis-(1,2,3-triazolyl)-appended benzimidazo [1,2-a]quinoline derivatives","volume":"185","author":"Macan","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112085","DOI":"10.1016\/j.ejmech.2020.112085","article-title":"Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities","volume":"190","author":"Sun","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8784","DOI":"10.1021\/acs.jmedchem.9b00942","article-title":"Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1)","volume":"62","author":"Reynaud","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Asemanipoor, N., Mohammadi-Khanaposhtani, M., Moradi, S., Vahidi, M., Asadi, M., Faramarzi, M.A., Mahdavi, M., Biglar, M., Larijani, B., and Hamedifar, H. (2020). Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential alpha-glucosidase inhibitors. Bioorganic Chem., 95.","DOI":"10.1016\/j.bioorg.2019.103482"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3390\/molecules28020733","article-title":"Recent Advances in N-Heterocyclic Small Molecules for Synthesis and Application in Direct Fluorescence Cell Imaging","volume":"28","author":"Li","year":"2023","journal-title":"Molecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1021\/acs.oprd.6b00156","article-title":"Identification and Control of Critical Process Impurities: An Improved Process for the Preparation of Dolutegravir Sodium","volume":"20","author":"Sankareswaran","year":"2016","journal-title":"Org. Process Res. Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/jhet.3588","article-title":"Preparation of Dolutegravir Intermediate Diastereomer","volume":"56","author":"Wang","year":"2019","journal-title":"J. Heterocycl. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1128\/jvi.62.9.3513-3516.1988","article-title":"Duck hepatitis B virus (DHBV) particles produced by transient expression of DHBV DNA in a human hepatoma cell line are infectious in vitro","volume":"62","author":"Pugh","year":"1988","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/0161-5890(82)90108-0","article-title":"Complement biosynthesis by the human hepatoma-derived cell line HepG2","volume":"19","author":"Morris","year":"1982","journal-title":"Mol. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hua, J., Wei, X., Li, Y., Li, L., Zhang, H., Wang, F., Zhang, C., and Ma, X. (2022). A Cyclen-Functionalized Cobalt-Substituted Sandwich-Type Tungstoarsenate with Versatility in Removal of Methylene Blue and Anti-ROS-Sensitive Tumor Cells. Molecules, 27.","DOI":"10.3390\/molecules27196451"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105129","DOI":"10.1016\/j.phrs.2020.105129","article-title":"Dolutegravir derivative inhibits proliferation and induces apoptosis of non-small cell lung cancer cells via calcium signaling pathway","volume":"161","author":"Wang","year":"2020","journal-title":"Pharmacol. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/8\/1779\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:27:43Z","timestamp":1760106463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/8\/1779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["molecules29081779"],"URL":"https:\/\/doi.org\/10.3390\/molecules29081779","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,13]]}}}