{"doi":"10.3390/molecules28124743","title":"Tricyclic Diterpenoids Selectively Suppress Androgen Receptor-Positive Prostate Cancer Cells","abstract":"Androgen receptor (AR) is a viable therapeutic target for lethal castration-resistant prostate cancer (CRPC), because the continued progression of CRPC is mainly driven by the reactivation of AR transcriptional activity. The current FDA-approved AR antagonists binding to ligand binding domain (LBD) become ineffective in CRPC with AR gene amplification, LBD mutation, and the evolution of LBD-truncated AR splice variants. Encouraged by the fact that tricyclic aromatic diterpenoid QW07 has recently been established as a potential N-terminal AR antagonist, this study aims to explore the structure–activity relationship of tricyclic diterpenoids and their potential to suppress AR-positive cell proliferation. Dehydroabietylamine, abietic acid, dehydroabietic acid, and their derivatives were selected, since they have a similar core structure as QW07. Twenty diterpenoids were prepared for the evaluation of their antiproliferative potency on AR-positive prostate cancer cell models (LNCaP and 22Rv1) using AR-null cell models (PC-3 and DU145) as comparisons. Our data indicated that six tricyclic diterpenoids possess greater potency than enzalutamide (FDA-approved AR antagonist) towards LNCaP and 22Rv1 AR-positive cells, and four diterpenoids are more potent than enzalutamide against 22Rv1 AR-positive cells. The optimal derivative possesses greater potency (IC50 = 0.27 µM) and selectivity than QW07 towards AR-positive 22Rv1 cells.","journal":"Molecules","year":2023,"id":370177,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":401921,"name":"Guanglin Chen","orcid":"0000-0002-5562-2320","position":1,"is_corresponding":false},{"id":1129330,"name":"Keyara Piri","orcid":"0000-0003-0084-7183","position":2,"is_corresponding":false},{"id":1129331,"name":"Seiji Shinkawa","orcid":"0000-0001-5435-2157","position":3,"is_corresponding":false},{"id":1129332,"name":"Dennis Ashong","orcid":"0000-0002-8941-6023","position":4,"is_corresponding":false},{"id":802611,"name":"Qiang Zhang","orcid":"0000-0003-3045-4444","position":5,"is_corresponding":false},{"id":321424,"name":"Guangdi Wang","orcid":"0000-0002-3999-8213","position":6,"is_corresponding":false},{"id":345125,"name":"Qiao‐Hong Chen","orcid":"0000-0001-6753-1824","position":7,"is_corresponding":false},{"id":1129716,"name":"Inderpal Sekhon","orcid":null,"position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T01:15:37.094100Z","pmid":"37375297","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":[]}