Antichlamydial Dimeric Indole Derivatives from Marine Actinomycete Rubrobacter radiotolerans

Abstract

Chlamydiae are widely distributed pathogens of human populations, which can lead to serious reproductive and other health problems. In our search for novel antichlamydial metabolites from marine derived-microorganisms, one new () and two known () dimeric indole derivatives were isolated from the sponge-derived actinomycete . The chemical structures of these metabolites were elucidated by NMR spectroscopic data as well as CD calculations. All three metabolites suppressed chlamydial growth in a concentration-dependent manner. Among them, compound exhibited the most effective antichlamydial activity with IC values of 46.6 ~ 96.4 µM in the production of infectious progeny. Compounds appeared to target the mid-stage of the chlamydial developmental cycle by interfering with reticular body replication, but not directly inactivating the infectious elementary body.

Pyocyanin Inhibits Chlamydia Infection by Disabling Infectivity of the Elementary Body and Disrupting Intracellular Growth

“…Although they are susceptible to several broad-spectrum antibiotics, clinical treatment failure is not uncommon. Without effective vaccines, there have been serious and continuous efforts to discover and develop new antichlamydials (4,(22)(23)(24)(25)(26)(27), particularly selective antichlamydials lacking adverse effects on the microbiota (4,22,23). In a search for natural compounds with antichlamydial activities, we identified pyocyanin as an antichlamydial with an IC 50 that is comparable to the IC 50 of tetracycline ( Fig.…”

“…Although extensive efforts have been devoted to vaccine development during the past few decades, no vaccine effective against human chlamydial diseases has been developed to date (20,21). These facts necessitate identification of novel antichlamydials through chemical synthesis (4,(22)(23)(24) and/or from natural sources (25)(26)(27).…”

In vitro Antichlamydial Activity of 1,2,3,5-Tetrasubstituted Pyrrole Derivatives

“…The antichlamydial effect of the compounds was evaluated as previously described and quantified by IC 50 between 1 and 32 μM [12, 15]. Cells directly seeded in 48-well plates were infected with Chlamydia at a multiplicity of infection of 0.2 inclusion-forming units (IFUs) per cell, and the individual compound was added simultaneously unless noted.…”

“…To avoid interference with the spectrometry-based assay by aggregation of aryl-substituted pyrroles [23], the cytotoxicity of the 1,2,3,5-tetrasubstituted pyrroles to the host cells was assessed by counting cell numbers after treatment with an individual compound to evaluate the cell proliferation activity [15]. HeLa cells cultured overnight, seeded on 24-well plates with about 20% confluence, were incubated with medium containing 32 µM of an individual compound or 0.5% DMSO.…”

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…cultivated from the marine ascidian S. brakenhielmi [ 139 ]; a azaphilonidal derivative penicilazaphilone C (MIC = 15.6 μg/mL) isolated from the marine fungus strain Penicillium sclerotiorum M-22 [ 140 ]; a new 2′-acetoxy-7-chlorocitreorosein anthraquinone (MIC = 10 μM) from a South China Sea endophytic marine fungus Penicillium citrinum HL-5126 [ 141 ]; a new antibacterial macrolide borrelidin C (MIC = 6 μM) from a saltern-derived holophilic Nocardiopsis sp. [ 142 ]; a new antichlamydial dimeric indole derivative (IC 50 = 46.6–96.4 μM) isolated from the South China Sea sponge-derived actinomycete Rubrobacter radiotolerans [ 143 ]; the anthraquinone emodin (MIC = 32 μg/mL) isolated from a culture of the endophytic fungus Eurotium chevalieri KUFA 0006 [ 144 ]; new thiodiketopiperazines eutypellazines P-R (MIC = 16–32 μM) isolated form a deep see fungus Eutypella sp. [ 145 ]; a new lipophilic cyclic hexapeptide thermoactinoamide A (MIC = 35 μM) isolated from the Icelandic thermophilic bacterium Thermoactinomyces vulgaris [ 146 ] ; and a new neo-actinomycin A (MIC = 16 μg/mL) isolated from a Chinese marine-derived Streptomyces sp.…”