{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kiichi Y"],"funding":["the Research Promotion Program for Acquiring KAKENHI, Ritsumeikan University","Japan Society for the Promotion of Science"],"pagination":["1389"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10976149"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(6)"],"pubmed_abstract":["Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at <i>N</i>-5 and <i>N</i>-9 yielded makaluvamine J and several analogs. A structure-activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at <i>N</i>-9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at <i>N</i>-5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog <b>24</b> showed potent and selective cytotoxicity (IC<sub>50</sub> = 0.029 µM, selective index = 13.1), exceeding those of natural products."],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs."],"pmcid":["PMC10976149"],"funding_grant_id":["22K05339","B21-0051"],"pubmed_authors":["Ishino K","Kiichi Y","Fukuoka K","Kotoku N","Kitano A"],"additional_accession":[]},"is_claimable":false,"name":"Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs.","description":"Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at <i>N</i>-5 and <i>N</i>-9 yielded makaluvamine J and several analogs. A structure-activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at <i>N</i>-9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at <i>N</i>-5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog <b>24</b> showed potent and selective cytotoxicity (IC<sub>50</sub> = 0.029 µM, selective index = 13.1), exceeding those of natural products.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-26T11:31:20.846Z","creation":"2025-04-06T13:41:02.731Z"},"accession":"S-EPMC10976149","cross_references":{"pubmed":["38543025"],"doi":["10.3390/molecules29061389"]}}