title: Analogues of the Inhoffen-Lythgoe diol with anti-proliferative activity.
abstract: The anti-proliferative activity of a series of ester- and amide-linked Inhoffen-Lythgoe side chain analogues is reported. Whereas the Inhoffen-Lythgoe diol was inactive in these studies, a number of aromatic and aliphatic ester-linked side chains demonstrated modest in vitro growth inhibition in two human cancepar cell lines, U87MG (glioblastoma) and HT-29 (colorectal adenocarcinoma). Structure-activity relationship (SAR) studies demonstrated the most active aromatic (13) and aliphatic (25 and 29) substituted analogues were approximately equipotent in U87MG and HT-29 cells. Further evaluation of 13, 25, and 29 indicated these analogues do not activate canonical vitamin D signaling nor antagonize Hedgehog (Hh) signaling. Thus, the cellular mechanism(s) that govern the anti-proliferative activity for this class of truncated vitamin D-based structures appears to be different from classical mechanisms previously identified for these scaffolds.
authors: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092, USA.
authors: Albert M
authors: AM
authors: DeBerardinis
authors: Steven
authors: S
authors: Lemieux
authors: M Kyle
authors: MK
authors: Hadden
mesh_terms: D000577:Amides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004952:Esters / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D007189:Indans / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000737:chemistry
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D004952:Esters; D007189:Indans; D014807:Vitamin D
keywords: Colon cancer; Glioblastoma; Inhoffen–Lythgoe diol; Vitamin D; Vitamin D receptor