Triple molecular target approach to selective melanoma cytotoxicity.
Phenylalanine-linked pyrrolo[1,2-a]benzimidazoles were successfully designed to target melanoma cells in vitro. Our design utilised three molecular targets: a phenylalanine pump, the reducing enzyme DT-diaphorase, and IMP dehydrogenase. We describe the synthesis of these compounds as well as the results of in vitro, in vivo, and QSAR studies.
Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA. eskibo@asu.edu
Edward B
EB
Skibo
Akmal
A
Jamil
Brittany
B
Austin
Douglas
D
Hansen
Armand
A
Ghodousi
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008958:Models, Molecular; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D021281:Quantitative Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011758:Pyrroles; D010649:Phenylalanine; C031000:benzimidazole; D007168:IMP Dehydrogenase