{"doi":"10.17615/scpj-rz78","title":"Inhibition of Human Acetyl- and Butyrylcholinesterase by Novel Carbamates of (−)- and (+)-Tetrahydrofurobenzofuran and Methanobenzodioxepine","abstract":"A new enantiomeric synthesis utilizing classical resolution provided two novel series of optically active inhibitors of cholinesterase: (−)- and (+)- O-carbamoyl phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two series of (−)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were obtained by known procedures, and their anticholinesterase actions were similarly quantified against freshly prepared human acetyl- (AChE) and butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated potent cholinesterase inhibitory activity (with IC50 values as low as 10 nM for AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of pyrroloindole that lacked activity (IC50 values > 1 µM). Based on the biological data of these four series, a SAR analysis was provided by molecular volume calculations. In addition, a probable transition state model was established according to the known X-ray structure of a transition state complex of Torpedo californica AChE-m-(N,N,N,trimethylammonio)-2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in explaining the enantio-selectivity and enzyme subtype selectivity of each series. These carbamates are more or similarly potent to anticholinesterases in current clinical use; providing not only inhibitors of potential clinical relevance but also pharmacological tools to define drug-enzyme binding interactions within an enzyme crucial in the maintenance of cognition and numerous systemic physiological functions in health, aging and disease.","journal":"INDIGO (University of Illinois at Chicago)","year":2020,"id":112168,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9424,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":188904,"name":"Arnold Brossi","orcid":null,"position":1,"is_corresponding":false},{"id":532450,"name":"Santosh S. Kulkarni","orcid":null,"position":2,"is_corresponding":false},{"id":532451,"name":"Damon A. Parrish","orcid":null,"position":3,"is_corresponding":false},{"id":532452,"name":"Harold W. Holloway","orcid":null,"position":4,"is_corresponding":false},{"id":305915,"name":"David Tweedie","orcid":"0000-0002-8446-4544","position":5,"is_corresponding":false},{"id":532453,"name":"Avigdor Shafferman","orcid":null,"position":6,"is_corresponding":false},{"id":360809,"name":"Weiming Luo","orcid":"0009-0002-3035-3176","position":7,"is_corresponding":false},{"id":532454,"name":"Qian‐sheng Yu","orcid":null,"position":8,"is_corresponding":false},{"id":278192,"name":"Debomoy K. Lahiri","orcid":"0000-0002-1664-5933","position":9,"is_corresponding":false},{"id":297917,"name":"Nigel H. Greig","orcid":"0000-0002-3032-1468","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:13.874980Z","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":[]}