{"doi":"10.1128/aac.00883-07","title":"Madurahydroxylactone Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and RNase H","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors.</jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2008,"id":644689,"datarank":1.6963737144676383,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":1.1468394675481912,"self_endowment_contribution":0.5495342469194471,"citer_contribution":1.1468394675481912,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":31,"citers_with_citation_signal":29,"citers_with_endowment":29,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":445219,"name":"John A. Beutler","orcid":"0000-0002-4646-1924","position":1,"is_corresponding":false},{"id":772115,"name":"Antony Wamiru","orcid":null,"position":2,"is_corresponding":false},{"id":1678193,"name":"Scott Budihas","orcid":null,"position":3,"is_corresponding":false},{"id":1678195,"name":"Ute Möllmann","orcid":null,"position":4,"is_corresponding":false},{"id":1678196,"name":"Lothar Heinisch","orcid":null,"position":5,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":6,"is_corresponding":false},{"id":1678197,"name":"Stuart F. Le Grice","orcid":null,"position":7,"is_corresponding":false},{"id":185421,"name":"Yves Pommier","orcid":null,"position":8,"is_corresponding":false},{"id":371393,"name":"Christophe Marchand","orcid":"0000-0002-0729-3841","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H.","abstract":"A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17967911","pmcid":"PMC2223906","openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"N01-CO-12400","title":null},{"funder_name":"NCI NIH HHS","grant_id":"N01 CO012400","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://doi.org/10.7270/q2c2507r","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Humans","HIV-1","Lactones","HIV Integrase","Enzyme Inhibitors","HIV Integrase Inhibitors","Anti-HIV Agents","Inhibitory Concentration 50","Structure-Activity Relationship","Ribonuclease H"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T01:50:02.263650Z","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":[]}