The obligate intracellular bacterium is a widespread human pathogen that causes serious problems, including (but not limited to) infertility and blindness. Our search for novel antichlamydial metabolites from marine-derived microorganisms led to the isolation of pyocyanin, a small compound from Pyocyanin is an effective antichlamydial for all three spp. tested. It has a 50% inhibitory concentration (IC) of 0.019 to 0.028 μM, which is comparable to the IC of tetracycline. At concentrations as low as 0.0039 μM, pyocyanin disables infectivity of the chlamydial elementary body (EB). At 0.5 μM or higher concentrations, the continuous presence of pyocyanin also inhibits chlamydial growth in the inclusion during later stages of the developmental cycle. Oxidative stress, a major known antimicrobial mechanism of pyocyanin, appears to be responsible only for the inhibition of bacterial growth and not for the disinfection of EBs. Pyocyanin is well-tolerated by probiotic vaginal spp. Our findings suggest that pyocyanin is of therapeutic value for chlamydial infections and can serve as a valuable chemical probe for studying chlamydial biology.

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

Background: Chlamydiae are widespread Gram-negative bacteria that cause a number of human diseases. Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen. </P><P> 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 &#181;M 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.