Xiaofeng Bao1, Ziyi Liu1, Min Ni1, Chao Xia1, Shunxin Xu1, Shengju Yang2, Yu Zhao1.
Abstract
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 of phenazine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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 of phenazine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
3-substituted phenazine; 3-substituted phenazine derivatives; Buchwald-Hartwig; antichlamydial activity; chlamydiae; synthesis.
Year: 2020
PMID： 31284867 DOI： 10.2174/1573406415666190708145639
Source DB: PubMed Journal: Med Chem ISSN： 1573-4064 Impact factor: 2.745