Novel quinoxaline antibiotics having the methylenedithioether bridge as an analogue of echinomycin have been synthesized by insertion of methylene moiety between -S-S- bond. The compound la shows remarkable cytotoxicities against human tumor various cell lines, and is active VRE (vancomycin-resistant enterococci) within MIC range 0.5-8 mug/mL. According to the eukaryotic or prokaryotic data, la might be a first analogue to replace echinomycin. (C) 2003 Elsevier Ltd. All rights reserved.