In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy.
To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.
Lim
Siang Hui
SH
Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
Thivierge
Cliferson
C
Nowak-Sliwinska
Patrycja
P
Han
Junyan
J
van den Bergh
Hubert
H
Wagnières
Georges
G
Burgess
Kevin
K
Lee
Hong Boon
HB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011162:Porphobilinogen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D026082:Singlet Oxygen / Q000378:metabolism; D013329:Structure-Activity Relationship
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D017319:Photosensitizing Agents; C507544:dipyrromethene; D026082:Singlet Oxygen; D011162:Porphobilinogen; D001895:Boron