Photochemical and photobiological properties of phenothiazine dyes and an analog of urocanic acid as potential anticancer and virucidal agents
Abstract
O-Methyl methylene violet (OMeMV), O-methyl bromomethylene violet (OMeBrMV), and O-methyl iodomethylene violet (OMeIMV) were prepared to improve upon the photoactive dyes, methylene violet (MV) and methylene blue (MB). All derivatives showed low quantum yields of fluorescence (<0.10) and the singlet lifetimes for OMeBrMV and OMeIMV were shortened relative to OMeMV. The quantum efficiencies for singlet oxygen formation were greater for OMeBrMV and OMeIMV than OMeMV (0.011). OMeMV N-demethyated upon irradiation. Non-covalent equilibrium constants (Kap) for OMeMV, OMeBrMV, and OMeIMV (all ∼1 × 105) binding to dsDNA were determined by Scatchard analysis of equilibrium dialysis data. Titration with dsDNA resulted in bathochromic shifts and hypochromic effects. OMeBrMV and OMeIMV (not OMeMV) covalently bound to DNA upon irradiation and there was no evidence of covalent binding in the dark. MV, OMeBrMV, and OMeIMV were about 10-fold more effective than OMeMV at photosensitizing KB cell death at 633 nm. The three dyes were also better than OMeMV at photoinactivating Sindbis virus in phosphate buffered saline (PBS). Fetal calf serum (25% FCS) changed the Sindbis inactivation rate by a factor of 0.25, 0.83, 0.48, and 0.4 for MV, OMeMV, OMeBrMV and OMeIMV respectively. [Rh(phen)(phi)Cl2]Cl was found to be more active in FCS than [Rh(phen) 2Cl2]Cl against photoinactivating Sindbis virus in both PBS and 25%. Imidazole-4(5)-methylidene malonic acid (IMMA), which lacks cis and trans identity, was prepared as an analog of urocanic acid (UA). The quantum efficiencies for decarboxylation and covalent binding to DNA (266 nm were ca 1 × 10−3 and 2.0 × 10−5, respectively. IMMA changed the rate of bacteriophage ssDNA inactivation by a factor of 0.43 and was intermediate between the E- and Z-UA isomers (1.6 and 0.01, respectively). IMMA sensitized the inactivation of double-stranded DNA similarly to UA.
Degree
Ph.D.
Advisors
Morrison, Purdue University.
Subject Area
Biochemistry|Pharmacology
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