Sj. Wagner et al., FACTORS AFFECTING VIRUS PHOTOINACTIVATION BY A SERIES OF PHENOTHIAZINE DYES, Photochemistry and photobiology, 67(3), 1998, pp. 343-349
A series of four phenothiazine dyes, including methylene blue (MB), we
re previously tested for their ability to photoinactivate viruses in r
ed cell suspensions. One of the dyes, methyl-3-dimethylamino-7-dimethy
laminophenotiazine (1,9-dimethylmethylene blue), exhibited good intrac
ellular and extracellular virucidal activity for several RNA and DNA v
iruses under conditions that minimally affected red cell properties. I
n order to understand why the virucidal specificity of 1,9-dimethylmet
hylene blue was greater than other phenothiazines tested, the physical
and chemical properties of the dye were compared to three other close
ly related analogues (MB, imethyl-3-diethylamino-7-dibutylaminophenoth
iazine [compound 4-140], methyl-3-dimethylamino-7-diethylaminophenothi
azine [compound 6-136]). All compounds required light and oxygen for v
irucidal activity and had relatively high singlet oxygen yields (>0.5)
, but 1,9-dimethylmethylene blue had a singlet oxygen yield approximat
ely 50% greater than that of MB. In addition, the hydrophobicity/hydop
hilicity of the compounds varied, with the partition coefficients (2-o
ctanol:water) ranging from 0.11 for MB to 3560 for compound 4-140. The
dyes had the following affinities for DNA:1,9-dimethylmethylene blue
> compound 6-136 > MB approximate to compound 4-140. This order was si
milar to the order of activities for photoinactivation of the nonenvel
oped bacteriophage, R17, by the four compounds. Results with the most
hydrophobic compound, 4-140, contrasted with those obtained with 1,9-d
imethylmethylene blue. Compound 4-140 had a high affinity for protein
and a low affinity for DNA. Although compound 4-140 and light inactiva
ted the nonenveloped bacteriophage R17 poorly, the dye readily photoin
activated enveloped viruses in buffer. However, unlike results with 1,
9-dlimethylmethylene blue, viral inactivation of enveloped viruses by
compound 4-140 was completely inhibited by the presence of red cells a
nd plasma. Thus, the high affinity of 1,9-dimethylmethylene blue for D
NA and the dye's efficient singlet oxygen yield suggest viral nucleic
acid as a potential target, which could explain the photosensitizer's
ability to Inactivate viruses without adversely affecting anucleate re
d cells.