Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on HDAC biology and antiproliferative activity.
A series of hydroxamic acid based histone deacetylase inhibitors 6-15, containing an isoxazole moiety adjacent to the Zn-chelating hydroxamic acid, is reported herein. Some of these compounds showed nanomolar activity in the HDAC isoform inhibitory assay and exhibited micro molar inhibitory activity against five pancreatic cancer cell lines.
Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Subhasish
S
Tapadar
Rong
R
He
Doris N
DN
Luchini
Daniel D
DD
Billadeau
Alan P
AP
Kozikowski
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007555:Isoxazoles; D006655:Histone Deacetylases; D015032:Zinc