Biophysical evaluation of two red-shifted hypocrellin B derivatives as novel PDT agents.
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/O2(.-) 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, LD(50) values for CHA2HB and DMAHB were found to be 0.1 microM and 1.5 microM, respectively. The singlet oxygen generating efficiency followed the order HB>CHA(2)HB>DMAHB. But, the enhanced red absorption as well as the hydrophilicity renders the CHA2HB a better photodynamic therapeutic agent.
Paul
Bibbin T
BT
Centre For Excellence in Genomic Science, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Babu
Mani S
MS
Santhoshkumar
Thankayyan R
TR
Karunagaran
Devarajan
D
Selvam
Govindan S
GS
Brown
Kevin
K
Woo
Thomas
T
Sharma
Sanjay
S
Naicker
Selvaraj
S
Murugesan
Ramachandran
R
D055592:Biophysical Phenomena; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003116:Color; D053837:DNA Cleavage; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D015394:Molecular Structure; D010100:Oxygen / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D011809:Quinones / Q000737:chemistry* / Q000494:pharmacology*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry; D014867:Water / Q000737:chemistry
D017319:Photosensitizing Agents; D011809:Quinones; D014867:Water; D013481:Superoxides; D010569:Perylene; D010100:Oxygen; C064522:hypocrellin B