title: Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human serum albumin binding properties of some novel bacteriochlorins.
abstract: The synthesis, photophysical characteristics, in vivo photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-a, have long-wavelength absorptions in the range lambda max = 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 vivo 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 vivo efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to bind to the diazepam binding site (albumin site II) and the in vivo photosensitizing efficacy.
authors.affiliation: Department of Radiation Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Pandey
authors.forename: S
authors.initials: S
authors.lastname: Constantine
authors.forename: T
authors.initials: T
authors.lastname: Tsuchida
authors.forename: G
authors.initials: G
authors.lastname: Zheng
authors.forename: C J
authors.initials: CJ
authors.lastname: Medforth
authors.forename: M
authors.initials: M
authors.lastname: Aoudia
authors.forename: A N
authors.initials: AN
authors.lastname: Kozyrev
authors.forename: M A
authors.initials: MA
authors.lastname: Rodgers
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: K M
authors.initials: KM
authors.lastname: Smith
authors.forename: T J
authors.initials: TJ
authors.lastname: Dougherty
mesh_terms: D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D008956:Models, Chemical; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D012709:Serum Albumin; C065423:bacteriochlorin a; D003975:Diazepam