Background: In the past century, many phenazines were isolated from the marine microorganism,
and some of these phenazines possessed potent antibacterial activities. We found that
a few of the synthesized 4-substituted phenazines could block the infectivity of chlamydiae without
host cell toxicity.
Objective: The aim of this study was to design and synthesize two series of novel 3-substituted
phenazines to find novel antichlamydial agents.
Methods: The 3-substituted phenazines were synthesized via Buchwald-Hartwig cross coupling
reaction and Suzuki reaction from 3-bromo-1-methoxyphenazine. The antichlamydial activity of
these synthesized compounds was evaluated by determining their effect on the yield of infectious
progeny EBs. Cytotoxicity of these compounds on host cells was assessed by the treatment of uninfected
HeLa cells using WST-1 method.
Results: Most of the 3-substituted phenazines possessed potent antichlamydial activity with IC50
values from 0.15 to 12.08 μM against Chlamydia trachomatis L2, C. muridarum MoPn and C.
pneumoniae AR39. Among them, 7d and 9a exhibited better antichlamydial activity with IC50 values
from 0.20 to 1.01 μM while they have no apparent cytotoxicity to host cells. Biological assay
disclosed that both 7d and 9a inhibited chlamydial infection by reducing elementary body infectivity
and disturbing chlamydial growth during the whole chlamydial developmental cycle.
Conclusion: Our findings suggested that 3-substituted phenazine derivatives might be a promising
class of therapeutic agents for chlamydial infections. More effective phenazines with low toxicity
could be acquired through further chemical modification on C-3 position rather than C-4 position