{"doi":"10.17615/js69-fg44","title":"Antitumor agents 294. Novel E-ring-modified camptothecin–4β-anilino-4′-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase I inhibitors and cytotoxic agents","abstract":"Two conjugates (1 and 2) of camptothecin (CPT) and 4β-anilino-4′-O-demethylepipodophyllotoxin were previously shown to exert antitumor activity through inhibition of topoisomerase I (topo I). In this current study, two novel conjugates (1E and 2E) with an open E-ring in the CPT moiety were first synthesized and evaluated for biological activity in comparison with their intact E-ring congeners. This novel class of CPT derivatives exhibits its antitumor effect against CPT-sensitive and -resistant cells, in part, by inhibiting topo I-linked DNA (TLD) religation. An intact E-ring was not essential for the inhibition of TLD religation, although conjugates with an open E-ring were less potent than the closed ring analogs. This lower religation potency resulted in decreased formation of protein-linked DNA breaks (PLDBs), and hence, less cell growth inhibition. In addition to their impact on topo I, conjugates 1E, 2, and 2E exhibited a minor inhibitory effect on topo II-induced DNA cleavage. The novel structures of 1E and 2E may present scaffolds for further development of dual function topo I and II inhibitors with improved pharmacological profiles and physicochemical properties.","journal":"UNC Libraries","year":2021,"id":212584,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":802831,"name":"Seung‐Whan Kim","orcid":"0000-0002-5899-2853","position":1,"is_corresponding":false},{"id":533166,"name":"Hao Zhu","orcid":"0000-0002-6507-8904","position":2,"is_corresponding":false},{"id":540868,"name":"Qian Shi","orcid":"0000-0002-2535-8119","position":3,"is_corresponding":false},{"id":802832,"name":"Chung‐Hang Leung","orcid":"0000-0003-2988-3786","position":4,"is_corresponding":false},{"id":802833,"name":"Shin‐Young Park","orcid":"0000-0002-6073-4634","position":5,"is_corresponding":false},{"id":802834,"name":"Deyong Ye","orcid":"0000-0003-0498-3019","position":6,"is_corresponding":false},{"id":244470,"name":"Susan L. Morris‐Natschke","orcid":"0000-0003-3772-0063","position":7,"is_corresponding":false},{"id":803497,"name":"Zao Li Jiang","orcid":null,"position":8,"is_corresponding":false},{"id":244476,"name":"Kuo‐Hsiung Lee","orcid":"0000-0002-6562-0070","position":9,"is_corresponding":false},{"id":579750,"name":"Elizabeth A. Gullen","orcid":null,"position":10,"is_corresponding":false},{"id":693357,"name":"Yung‐Chi Cheng","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:52:27.434608Z","pmid":null,"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":[]}