title: In vitro photodynamic therapy and quantitative structure-activity relationship studies with stable synthetic near-infrared-absorbing bacteriochlorin photosensitizers.
abstract: 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.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Huang
authors.forename: Pawel
authors.initials: P
authors.lastname: Mroz
authors.forename: Timur
authors.initials: T
authors.lastname: Zhiyentayev
authors.forename: Sulbha K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Thiagarajan
authors.initials: T
authors.lastname: Balasubramanian
authors.forename: Christian
authors.initials: C
authors.lastname: Ruzié
authors.forename: Michael
authors.initials: M
authors.lastname: Krayer
authors.forename: Dazhong
authors.initials: D
authors.lastname: Fan
authors.forename: K Eszter
authors.initials: KE
authors.lastname: Borbas
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Yang
authors.forename: Hooi Ling
authors.initials: HL
authors.lastname: Kee
authors.forename: Christine
authors.initials: C
authors.lastname: Kirmaier
authors.forename: James R
authors.initials: JR
authors.lastname: Diers
authors.forename: David F
authors.initials: DF
authors.lastname: Bocian
authors.forename: Dewey
authors.initials: D
authors.lastname: Holten
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: 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
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin