ABSTRACT
A panel of new potential Ras ligands was generated by decorating a tricyclic levoglucosenone-derived scaffold with aromatic moieties. Some members of the panel show in vitro inhibitory activity toward the nucleotide exchange process on Ras and are toxic to some human cancer cell lines.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Drug Design , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Glucose/analogs & derivatives , ras Proteins/antagonists & inhibitors , Animals , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Cell Line , Cell Proliferation/drug effects , Enzyme Inhibitors/chemistry , Glucose/chemical synthesis , Glucose/chemistry , Glucose/pharmacology , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , ras Proteins/metabolismABSTRACT
A bicyclic scaffold derived from the natural monosaccharide d-glucose, and possessing several diversity sites, was linked to various resins through the primary (C-6) hydroxyl and decorated on the solid phase: the hydroxyl group at C-4 was functionalized as ester, ether, and carbamate, the amino group in the second cycle (C-3' position) was functionalized as amide, sulfonamide, and ureido- and thioureido-derivatives. The compounds synthesized on the solid phase were tested for their antiproliferative activity on tumor cell lines.
