Isolation, Structure Determination, and Semisynthesis of Diphenazine Compounds from a Deep-Sea-Derived Strain of the Fungus Cystobasidium laryngis and Their Biological Activities

Journal of Natural Products
2022.0

Abstract

Phenazostatins E-J (<b>1</b>-<b>6</b>), six new diphenazine derivatives, were isolated from the EtOAc extract of the culture broth of a strain of <i>Cystobasidium laryngis</i> derived from deep-sea sediments of the Indian Ocean Ridge. The structures of <b>1</b>-<b>6</b> were elucidated based on the HRESIMS and 1D and 2D NMR spectra. The absolute configurations of <b>1</b>-<b>6</b>, except for <b>3</b> and <b>6</b>, were determined by modified Mosher's method, ECD data analysis, and calculations of optical rotation values. The absolute configurations of <b>3</b> and <b>6</b> were identified by chemical derivatization and comparing the specific rotation values with those of semisynthetic <b>3</b> obtained by the oxidation of <b>1</b> and saphenic acid (<b>7</b>). Phenazostatin J (<b>6</b>) was semisynthesized using saphenic acid (<b>7</b>) to prepare additional material for biological testing. During the purification of semisynthetic <b>6</b>, a side product <b>9</b> was obtained from the reaction mixture along with <b>6</b>. Compounds <b>1</b>-<b>6</b>, along with previously reported <b>7</b> and <b>8</b>, were assessed for anti-neuroinflammatory activity in LPS-induced BV-2 microglia cells. Compound <b>6</b> exhibited the highest anti-neuroinflammatory effect with an IC<sub>50</sub> value of 0.30 μM, but it showed cytotoxicity at higher concentrations than 1.0 μM. Accordingly, cytotoxicities of <b>1</b>-<b>9</b> were evaluated against six human cancer cell lines. Among tested compounds, <b>6</b> and <b>9</b> showed potent cytotoxicity (IC<sub>50</sub> values: 7.7-72 nM). Especially, <b>6</b> exhibited the strongest cytotoxicity with an IC<sub>50</sub> value of 7.7 nM against the NUGC-3 (stomach) cell line, displaying 19-fold stronger activity than the positive control, adriamycin.

Knowledge Graph

Similar Paper

Isolation, Structure Determination, and Semisynthesis of Diphenazine Compounds from a Deep-Sea-Derived Strain of the Fungus Cystobasidium laryngis and Their Biological Activities
Journal of Natural Products 2022.0
Phenazine Derivatives with Anti-Inflammatory Activity from the Deep-Sea Sediment-Derived Yeast-Like Fungus Cystobasidium laryngis IV17-028
Marine Drugs 2019.0
New Diphenazines with Neuronal Cell Protecting Activity, Phenazostatins A and B, Produced by Streptomyces sp.
The Journal of Antibiotics 1997.0
Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo
Journal of Natural Products 2024.0
Phenazostatin C, a New Diphenazine with Neuronal Cell Protecting Activity from Streptomyces sp.
The Journal of Antibiotics 1999.0
Cytotoxic and antimicrobial benzodiazepine and phenolic metabolites from Aspergillus ostianus<scp>IMBC‐NMTP03</scp>
Vietnam Journal of Chemistry 2021.0
Cytotoxic Nitrogenated Azaphilones from the Deep-Sea-Derived Fungus <i>Chaetomium globosum</i> MP4-S01-7
Journal of Natural Products 2020.0
Dichotocejpins A–C: New Diketopiperazines from a Deep-Sea-Derived Fungus Dichotomomyces cejpii FS110
Marine Drugs 2016.0
Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.
Molecules 2016.0
Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.
Molecules 2016.0