{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:55:15Z","timestamp":1778943315889,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["CHE-1900509"],"award-info":[{"award-number":["CHE-1900509"]}]},{"name":"National Science Foundation","award":["CHE-1828399"],"award-info":[{"award-number":["CHE-1828399"]}]},{"name":"National Science Foundation","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"DOI":"10.13039\/100000002","name":"MSK Core Center","doi-asserted-by":"publisher","award":["CHE-1900509"],"award-info":[{"award-number":["CHE-1900509"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"MSK Core Center","doi-asserted-by":"publisher","award":["CHE-1828399"],"award-info":[{"award-number":["CHE-1828399"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"MSK Core Center","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The high potency of the tetrahydrofuran-containing acetogenins (THF-ACGs) against a broad range of human cancer cell lines has stimulated interest in structurally simpler mimetics. In this context, we have previously reported THF-ACG mimetics in which the THF and butenolide moieties of a mono-THF-ACG were replaced with carbohydrate and thiophene residues, respectively. In the present study, towards the targeting of these carbohydrate analogues to prostate cancer (PCa), we synthesized prodrugs in which a parent thiophene or butenolide congener was conjugated through a self-immolative linker to 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA), a highly specific ligand for prostate-specific membrane antigen (PSMA), which is overexpressed on prostate tumors. Both prodrugs were found to be more active against receptor positive LNCaP than receptor-negative PC-3 cells, with 2.5 and 12 times greater selectivity for the more potent thiophene analog and the less active butenolide congener, respectively. This selectivity for LNCaP over PC-3 contrasted with the behavior of the parent drugs, which showed similar or significantly higher activity for PC-3 compared to LNCaP. These data support the notion that higher activity of these DUPA-derived prodrugs against LNCaP cells is connected to their binding to PSMA and suggest that the conjugation of PSMA ligands to this family of cytotoxic agents may be effective for targeting them to PCa.<\/jats:p>","DOI":"10.3390\/molecules28072884","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T02:34:54Z","timestamp":1679625294000},"page":"2884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting Carbohydrate Mimetics of Tetrahydrofuran-Containing Acetogenins to Prostate Cancer"],"prefix":"10.3390","volume":"28","author":[{"given":"Patricia Gonzalez","family":"Periche","sequence":"first","affiliation":[{"name":"Department of Chemistry, Hunter College and The Graduate Center, City University of New York, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacky","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hunter College and The Graduate Center, City University of New York, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naga V. S. D. K.","family":"Bhupathiraju","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hunter College and The Graduate Center, City University of New York, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0210-0270","authenticated-orcid":false,"given":"Teja","family":"Kalidindi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delissa S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagavarakishore","family":"Pillarsetty","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5159-1299","authenticated-orcid":false,"given":"David R.","family":"Mootoo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hunter College and The Graduate Center, City University of New York, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1021\/np980406d","article-title":"Annonaceous acetogenins: Recent progress","volume":"62","author":"Alali","year":"1999","journal-title":"J. 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