In vitro photodynamic therapy and quantitative structure-activity relationship studies with stable synthetic near-infrared-absorbing bacteriochlorin photosensitizers.
Photodynamic therapy (PDT) is a rapidly developing approach to treating cancer that combines harmless visible and near-infrared light with a nontoxic photoactivatable dye, which upon encounter with molecular oxygen generates the reactive oxygen species that are toxic to cancer cells. Bacteriochlorins are tetrapyrrole compounds with two reduced pyrrole rings in the macrocycle. These molecules are characterized by strong absorption features from 700 to >800 nm, which enable deep penetration into tissue. This report describes testing of 12 new stable synthetic bacteriochlorins for PDT activity. The 12 compounds possess a variety of peripheral substituents and are very potent in killing cancer cells in vitro after illumination. Quantitative structure-activity relationships were derived, and subcellular localization was determined. The most active compounds have both low dark toxicity and high phototoxicity. This combination together with near-infrared absorption gives these bacteriochlorins great potential as photosensitizers for treatment of cancer.
Huang
Ying-Ying
YY
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.
Mroz
Pawel
P
Zhiyentayev
Timur
T
Sharma
Sulbha K
SK
Balasubramanian
Thiagarajan
T
Ruzié
Christian
C
Krayer
Michael
M
Fan
Dazhong
D
Borbas
K Eszter
KE
Yang
Eunkyung
E
Kee
Hooi Ling
HL
Kirmaier
Christine
C
Diers
James R
JR
Bocian
David F
DF
Holten
Dewey
D
Lindsey
Jonathan S
JS
Hamblin
Michael R
MR
D016923:Cell Death / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007259:Infrared Rays; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin