{"doi":"10.1002/cmdc.202400932","title":"Resorcinol‐based Bolaamphiphilic Quaternary Ammonium Compounds","abstract":"Quaternary ammonium compounds (QACs) play crucial disinfectant roles in healthcare, industry, and domestic settings. Most commercially utilized QACs like benzalkonium chloride have a common architectural theme, leading to a rise in bacterial resistance and urgent need for novel structural classes. Some potent QACs such as chlorhexidine (CHX) and octenidine (OCT) feature a bolaamphiphilic architecture, comprised of two cationic centers at the molecular periphery and a non-polar region connecting them; these compounds show promise to elude bacterial resistance mechanisms. Inspired by such structures, we synthesized a series of 43 biscationic amphiphilic compounds focused on a resorcinol core, featuring flexibility of linker lengths, alkyl tails, and relative substituent positioning, to study their structure activity relationships (SARs). Antibacterial activity evaluation against a panel of gram-positive and gram-negative strains, including ESKAPE pathogens (A. baumannii, P. aeruginosa), were encouraging, with minimum inhibitory concentrations (MICs) of 0.5-4 μM against all tested strains for select compounds. Ten prepared compounds bearing either 17 or 18 total side chain carbons demonstrated uniformly strong antibacterial activity against P. aeruginosa (MIC 4-16 μM) and 6 other strains (MIC ≤4 μM), irrespective of cationic spacing. These findings promise to further extend the application of bolaamphiphilic QACs as a novel class of disinfectants.","journal":"ChemMedChem","year":2025,"id":516894,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9642,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1383256,"name":"C.P. Casey","orcid":null,"position":1,"is_corresponding":false},{"id":1252520,"name":"Elise L. Bezold","orcid":"0009-0002-2721-284X","position":2,"is_corresponding":false},{"id":1383257,"name":"Asantha Fernando","orcid":null,"position":3,"is_corresponding":false},{"id":1372452,"name":"Diana McDonough","orcid":null,"position":4,"is_corresponding":false},{"id":381167,"name":"William M. Wuest","orcid":"0000-0002-5198-7744","position":5,"is_corresponding":false},{"id":710168,"name":"Kevin P. C. Minbiole","orcid":"0000-0003-4263-9833","position":6,"is_corresponding":false},{"id":1383255,"name":"Johanna Y. D. Asante","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39822143","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":[]}