title: Synthesis and in vitro and in vivo evaluation of a series of dihydroisocoumarin derivatives conjugated with fatty acids, alcohols, and amines as potential anticancer agents.
abstract: In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to the dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds conjugated with gamma-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1,3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo in a number of human tumor xenograft models.
authors.affiliation: Centre for Cancer Research and Cell Biology (CCRCB), Queens University Belfast, Belfast, Northern Ireland, BT9 7BL, United Kingdom. c.a.higgins@qub.ac.uk
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Higgins
authors.forename: Zoica
authors.initials: Z
authors.lastname: Delbederi
authors.forename: Kelly
authors.initials: K
authors.lastname: McGarel
authors.forename: Timothy
authors.initials: T
authors.lastname: Mills
authors.forename: Owen
authors.initials: O
authors.lastname: McGrath
authors.forename: Stephanie
authors.initials: S
authors.lastname: Feutren-Burton
authors.forename: William
authors.initials: W
authors.lastname: Watters
authors.forename: Paul
authors.initials: P
authors.lastname: Armstrong
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Johnston
authors.forename: David
authors.initials: D
authors.lastname: Waugh
authors.forename: Hendrik
authors.initials: H
authors.lastname: van den Berg
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005227:Fatty Acids / Q000737:chemistry; D006801:Humans; D049934:Isocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000438:Alcohols; D000588:Amines; D000970:Antineoplastic Agents; D005227:Fatty Acids; D049934:Isocoumarins