A class of novel AA-Trp-Trp-OBzl: synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and intercalation mechanism

From the anti-tumoral active N-tryptophanyl-beta-carboline-3-carboxylic acid benzyl ester and beta-carboline-3-carbonyltryptophan benzyl ester, an anti-tumoral pharmacophore, Trp-Trp-OBzl, was drawn. Into the N-terminus of Trp-Trp-OBzl, L-amino acids were introduced and twenty AA-Trp-Trp-OBzls were provided. The automated docking studies showed AA-Trp-Trp-OBzls to be desirable intercalators. The in vitro and in vivo assays explored that thirteen of twenty AA-Trp-Trp-OBzls were anti-tumoral active, and nine of twenty AA-Trp-Trp-OBzls were more active than cytarabine. The acute toxicity, spleen index and increased body weight demonstrated that AA-Trp-Trp-OBzls did not damage the immunologic function of the treated mice and had a LD(50) value of more than 500 mg kg(-1). DNA intercalation was considered the action mechanism of Asn-Trp-Trp-OBzl.