Synthesis of bis-1,2,3-triazolo-bridged unsymmetrical pyrrolobenzodiazepine trimers via 'click' chemistry and their DNA-binding studies

New conceivable synthetic approach for the construction of nitrogen-rich 1,2,3-triazolo-pyrrolo[2,1-c] [1,4]benzodiazepine (TPBD, 3a-c) trimers has been developed. The first example of a bis-1,2,3-triazolo-bridged unsymmetrical PBD trimer has been successfully synthesized by employing a CuAAC type 'click' chemistry protocol. This efficient route generates tri-imine functionality in a single molecule. It has been envisaged that such tri-imine functionalities could bring in efficient interaction with DNA in a sequence-selective manner in the minor groove of duplex DNA. One of the representative analogues 3c has shown improved DNA-binding ability (Delta T(m) 23.7 degrees C) by thermal denaturation studies using CT-DNA and this data is also supported by molecular modeling (MD) studies. (C) 2010 Elsevier Ltd. All rights reserved.