Two novel cyclohexane-1,2-diamino and N,N dimethyl amino-propyl substituted hypocrellin B derivatives, abbreviated as CHA2HB and DMAHB, respectively were synthesized. These derivatives exhibited enhanced absorption in phototherapeutic window. Photodynamic action of these derivatives, investigated using optical and electron spin resonance methods, depended on both Type I and Type II mechanisms. Gel electrophoresis indicated 1O2/O2radical dot - mediated DNA damage. CHA2HB displayed 20 fold increase in light dependent cytotoxicity on colon cancer cell line (HCT 116) than the well-known hypocrellin B (HB). The light induced, LD50 values for CHA2HB and DMAHB were found to be 0.1 μM and 1.5 μM, respectively. The singlet oxygen generating efficiency followed the order HB > CHA2HB > DMAHB. But, the enhanced red absorption as well as the hydrophilicity renders the CHA2HB a better photodynamic therapeutic agent. © 2008 Elsevier B.V. All rights reserved.