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European journal of medicinal chemistry

A class of Trp-Trp-AA-OBzl: Synthesis, inxa0vitro anti-proliferation/inxa0vivo anti-tumor evaluation, intercalation-mechanism investigation and 3D QSAR analysis.


PMID 21620529

Abstract

From the anti-tumor active N-tryptophanyl-β-carboline-3-carboxylic acid benzyl ester and β-carboline-3-carbonyltryptophan benzyl ester, a pharmacophore, Trp-Trp-OBzl, was drawn. Based on the DOCK scores amino acid residue was inserted into the C-terminus of Trp-Trp-OBzl and twenty Trp-Trp-AA-OBzls (AAxa0=xa0amino acid residues) were provided as DNA intercalators. On the inxa0vitro and inxa0vivo models seventeen Trp-Trp-AA-OBzls were anti-tumor active, and twelve Trp-Trp-AA-OBzls were more active than cytarabine. In acute toxicity assay Trp-Trp-AA-OBzls did not damage the immunologic function and had an LD(50) of more than 500xa0mg/kg. The relationships of structure and activity were analyzed with 3D QSAR. The action mechanism studies revealed that the inxa0vivo anti-tumor action of Trp-Trp-AA-OBzls was the result of DNA intercalation.