{"doi":"10.1016/j.chembiol.2024.09.007","title":"Quinoline-based compounds can inhibit diverse enzymes that act on DNA","abstract":"DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation. Additionally, some quinoline-based analogs inhibit other DNA-interacting enzymes, such as polymerases and base excision repair glycosylases. Finally, compound 11 elicits DNA damage response via p53 activation in cancer cells.","journal":"Cell chemical biology","year":2024,"id":443493,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1029216,"name":"Qin Chen","orcid":"0000-0003-1821-2776","position":1,"is_corresponding":false},{"id":362021,"name":"Ren Ren","orcid":"0000-0001-8288-8012","position":2,"is_corresponding":false},{"id":647920,"name":"Jie Yang","orcid":"0000-0003-2241-5066","position":3,"is_corresponding":false},{"id":389781,"name":"Bigang Liu","orcid":null,"position":4,"is_corresponding":false},{"id":356766,"name":"J.R. Horton","orcid":"0000-0001-9749-8068","position":5,"is_corresponding":false},{"id":748383,"name":"Caleb Chang","orcid":"0000-0002-4507-659X","position":6,"is_corresponding":false},{"id":909314,"name":"Chuxuan Li","orcid":"0000-0001-9386-9909","position":7,"is_corresponding":false},{"id":909835,"name":"Leora Maksoud","orcid":null,"position":8,"is_corresponding":false},{"id":695680,"name":"Yifei Yang","orcid":"0000-0001-7134-3623","position":9,"is_corresponding":false},{"id":295618,"name":"Dante Rotili","orcid":"0000-0002-8428-8763","position":10,"is_corresponding":false},{"id":277805,"name":"Abhinav K. Jain","orcid":"0000-0003-3268-514X","position":11,"is_corresponding":false},{"id":288979,"name":"Xing Zhang","orcid":"0000-0002-2699-3448","position":12,"is_corresponding":false},{"id":356768,"name":"Robert Blumenthal","orcid":"0000-0002-0873-0724","position":13,"is_corresponding":false},{"id":432260,"name":"Taiping Chen","orcid":"0000-0002-2524-6440","position":14,"is_corresponding":false},{"id":678959,"name":"Yang Gao","orcid":"0000-0002-4037-0431","position":15,"is_corresponding":false},{"id":302737,"name":"Sérgio Valente","orcid":"0000-0002-2241-607X","position":16,"is_corresponding":false},{"id":111037,"name":"Antonello Mai","orcid":"0000-0001-9176-2382","position":17,"is_corresponding":false},{"id":356553,"name":"Xiaodong Cheng","orcid":"0000-0002-6967-6362","position":18,"is_corresponding":false},{"id":356767,"name":"Jujun Zhou","orcid":"0000-0003-4104-7158","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39437789","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}