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dc.contributor.authorIbrahim, Ali I.M.
dc.contributor.authorBattle, Elisabet
dc.contributor.authorSneha, Smarakan
dc.contributor.authorJimenez, R.
dc.contributor.authorPequerul, R.
dc.contributor.authorPares, X.
dc.contributor.authorRüngeler, T.
dc.contributor.authorJha, V.
dc.contributor.authorTuccinardi, T.
dc.contributor.authorSadiq, Maria
dc.contributor.authorFrame, F.
dc.contributor.authorMaitland, N.J.
dc.contributor.authorFarres, J.
dc.contributor.authorPors, Klaus
dc.date.accessioned2022-04-28T13:00:44Z
dc.date.accessioned2022-04-29T07:06:47Z
dc.date.available2022-04-28T13:00:44Z
dc.date.available2022-04-29T07:06:47Z
dc.date.issued2022-03-10
dc.identifier.citationIbrahim AIM, Battle E, Sneha S et al (2022) Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer. Journal of Medicinal Chemistry. 65(5): 3833-3848.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18949
dc.descriptionYesen_US
dc.description.abstractAldehyde dehydrogenases (ALDHs) are overexpressed in various tumor types including prostate cancer and considered a potential target for therapeutic intervention. 4-(Diethylamino)benzaldehyde (DEAB) has been extensively reported as a pan-inhibitor of ALDH isoforms, and here, we report on the synthesis, ALDH isoform selectivity, and cellular potencies in prostate cancer cells of 40 DEAB analogues; three analogues (14, 15, and 16) showed potent inhibitory activity against ALDH1A3, and two analogues (18 and 19) showed potent inhibitory activity against ALDH3A1. Significantly, 16 analogues displayed increased cytotoxicity (IC50 = 10-200 μM) compared with DEAB (>200 μM) against three different prostate cancer cell lines. Analogues 14 and 18 were more potent than DEAB against patient-derived primary prostate tumor epithelial cells, as single agents or in combination treatment with docetaxel. In conclusion, our study supports the use of DEAB as an ALDH inhibitor but also reveals closely related analogues with increased selectivity and potency.en_US
dc.description.sponsorshipS12-027/PCUK_/Prostate Cancer UK/United Kingdomen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1021/acs.jmedchem.1c01367en_US
dc.rights(c) 2022 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectCellsen_US
dc.subjectAldehydesen_US
dc.subjectInhibitionen_US
dc.subjectInhibitorsen_US
dc.subjectCanceren_US
dc.titleExpansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Canceren_US
dc.status.refereedYesen_US
dc.date.Accepted2022-01-17
dc.date.application2022-02-25
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.rights.licenseCC-BYen_US
dc.date.updated2022-04-28T13:00:47Z
refterms.dateFOA2022-04-29T07:11:38Z
dc.openaccess.statusopenAccessen_US


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