Additive effect of heparin on the photoinactivation of Escherichia coli using tricationic P-porphyrins

Bioorganic and Medicinal Chemistry Letters

4 years ago

Additive effect of heparin on the photoinactivation of Escherichia coli using tricationic P-porphyrins

Polycationic porphyrins have received substantial attention in developing singlet oxygen-sensitizers for biological use such as in the photoinactivation of bacteria and photodynamic therapy (PDT) of tumor cells because they have strong binding affinities for DNA and proteins. However, these strong cellular interactions can retard elimination of the drug after PDT. Therefore, the studies on the interactions of porphyrins with other molecules present much interest, in order to modulate the sensitizers‘ activity or even remove them from the human body after PDT. Here, we studied the additive effect of heparin on the photoinactivation by polycationic porphyrins using Escherichia coli as a model cell. Tricationic P-porphyrin sensitizers substituted with an N-alkylpyridinium group (alkyl = pentyl (1a), hexyl (1b), and heptyl (1c)) or N-hexylammonium (1d) as the axial ligand were used. Additionally, dicationic Sb-porphyrin substituted with an N-hexylpyridinium group (1e) was prepared. We studied the additive effect of heparin on the photoinactivation of E. coli by 1a-1e. The bactericidal activities were evaluated using the half-life (T 1/2 in min) of E. coli and the minimum effective concentrations ([P]) of the porphyrin sensitizers. In the absence of heparin, the [P] values were determined to be 0.4 - 0.5μM for 1a−1c and 2.0 μM for 1d−1e. The bactericidal activity of 1a−1c was completely retarded by the addition of heparin (1.0 μM). However, the addition of heparin (1.0 μM) could not completely retard the bactericidal activity of 1d−1e whose [P] values were relatively large. It is suggested that tricationic 1a−1c adsorbed onto the anionic heparin through electrostatic interactions. The adsorption of 1 on heparin disturbs the uptake of 1 into E. coli cells. Thus, the addition of heparin was found to be a useful method for retarding photoinactivation.

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DOI: S0960894X1731017X