Structure-activity relationship among purpurinimides and bacteriopurpurinimides: trifluoromethyl substituent enhanced the photosensitizing efficacy.
At similar lipophilicity, compared to the nonfluorinated purpurinimide 11, the corresponding fluorinated analog 8 with a trifluoromethyl substituent at the lower half (position-132) of the molecule showed enhanced photosensitizing efficacy. The structural parameters established in purpurinimides (lambdamax: 700 nm) were successfully translated to the bacteriopurpurin imide system 19 (lambdamax: 792 nm) and within both series, a monotonic relationship between the lipophilicity and the in vivo PDT activity was observed. For preparing water-soluble compounds, the photosensitizers 8 and 19 were converted into the corresponding aminobenzyl-diethylenetriamine pentaacetate conjugates 23 and 26. Acid treatment of purpurinimide 23 produced the corresponding water-soluble analog 24. Bacteriochlorin 26 under acidic or basic conditions mainly gave the decomposition products. At similar in vivo treatment conditions (C3H mice with RIF tumors and BALB-C mice with colon-26 tumors) the water-soluble purpurinimide 24 was found to be more effective than the methyl ester analog 8. These results suggest that besides overall lipophilicity the inherent charge of the photosensitizer also influences the PDT efficacy.
Gryshuk
Amy
A
Chemistry Division, PDT Center, and Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Chen
Yihui
Y
Goswami
Lalit N
LN
Pandey
Suresh
S
Missert
Joseph R
JR
Ohulchanskyy
Tymish
T
Potter
William
W
Prasad
Paras N
PN
Oseroff
Allan
A
Pandey
Ravindra K
RK
D000818:Animals; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005461:Fluorine; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012242:Rhodobacter sphaeroides / Q000737:chemistry; D012995:Solubility; D053545:Spirulina / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014867:Water
D007094:Imides; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; D005461:Fluorine