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.
Skibo
Edward B
EB
Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA. eskibo@asu.edu
Jamil
Akmal
A
Austin
Brittany
B
Hansen
Douglas
D
Ghodousi
Armand
A
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