Synthesis and Antichlamydial Activity of Novel Phenazines

Author(s): Xiaofeng Bao, Xiaowei Yu, Chao Xia, Ningjing Yang, Shengju Yang*, Yu Zhao*.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 2 , 2019

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Abstract:

Abstract: Background: Chlamydiae are widespread Gram-negative bacteria that cause a number of human diseases. Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen.

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 developmental cycle.

Conclusion: Our findings suggest C-4 aryl and C-4 amino phenazine derivatives as promising lead molecules for antichlamydials development.

Keywords: Phenazine, synthesis, antichlamydial activity, Buchwald-Hartwig, chlamydia, elementary body.

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Article Details

VOLUME: 16
ISSUE: 2
Year: 2019
Page: [174 - 181]
Pages: 8
DOI: 10.2174/1570180815666180518112952
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