TY - JOUR
T1 - Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human serum albumin binding properties of some novel bacteriochlorins
AU - Pandey, Ravindra K.
AU - Constantine, Scott
AU - Tsuchida, Takaaki
AU - Zheng, Gang
AU - Medforth, Craig J.
AU - Aoudia, Mohamed
AU - Kozyrev, Andrei N.
AU - Rodgers, Michael A.J.
AU - Kato, Harubumi
AU - Smith, Kevin M.
AU - Dougherty, Thomas J.
PY - 1997/8/15
Y1 - 1997/8/15
N2 - The synthesis, photophysical characteristics, in vive photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-α, have long-wavelength absorptions in the range λmax = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol- pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively low fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in vive studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vive efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to hind to the diazepam binding site (albumin site II) and the in vive photosensitizing efficacy.
AB - The synthesis, photophysical characteristics, in vive photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-α, have long-wavelength absorptions in the range λmax = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol- pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively low fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in vive studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vive efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to hind to the diazepam binding site (albumin site II) and the in vive photosensitizing efficacy.
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U2 - 10.1021/jm9702894
DO - 10.1021/jm9702894
M3 - Article
C2 - 9276023
AN - SCOPUS:14444287274
SN - 0022-2623
VL - 40
SP - 2770
EP - 2779
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 17
ER -