Abstract: Background: Chlamydiae are widespread Gram-negative bacteria that cause a
number of human diseases. Chlamydia trachomatis is the most prevalent sexually transmitted bacterial
Methods: Fourteen novel phenazine derivatives were efficiently synthesized via Buchwald-Hartwig
cross coupling reaction and Suzuki reaction from 4-bromo-1-methoxyphenazine. All the derivatives
displayed antichlamydial activity with IC50 values from 1.01-19.77 µM against Chlamydia trachomatis
D and L2 for inhibiting progeny formation.
Results: C-4 morpholinyl 8a and C-4 phenyl phenazine 9c exhibited stronger antichlamydial activity
with no apparent cytotoxicity. Both phenazine derivatives inhibited chlamydial inclusions formation
and growth in a dose-dependent manner. They inhibited Chlamydia infection by reducing
elementary body infectivity and disturbing Chlamydia growth at the mid-stage of the chlamydial
Conclusion: Our findings suggest C-4 aryl and C-4 amino phenazine derivatives as promising lead
molecules for antichlamydials development.