Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human serum albumin binding properties of some novel bacteriochlorins

J Med Chem. 1997 Aug 15;40(17):2770-9. doi: 10.1021/jm9702894.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Chromatography, High Pressure Liquid
  • Diazepam / metabolism
  • Female
  • Humans
  • Mice
  • Mice, Inbred DBA
  • Models, Chemical
  • Neoplasms, Experimental / drug therapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / metabolism
  • Porphyrins / chemistry*
  • Porphyrins / metabolism
  • Protein Binding
  • Serum Albumin / metabolism*
  • Spectrophotometry, Atomic

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Serum Albumin
  • bacteriochlorin a
  • Diazepam