Ethylnaphthoquinone derivatives as inhibitors of indoleamine-2, 3-dioxygenase from the mangrove endophytic fungus Neofusicoccum austral SYSU-SKS024

Cui, Hui; Zhang, Hongao; Liu, Yena; Gu, Qiong; Xu, Jun; Huang, Xishan; She, Zhigang

doi:10.1016/j.fitote.2018.01.014

Cited by 17 publications

(10 citation statements)

References 24 publications

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“…Only TD34 inhibited kynurenine production at 20 µM (Figure 6A) in the absence of cell toxicity. Interestingly, TD34 shares similarity with previously reported ethylnaphthoquinone derivatives, inhibitors of IDO1 [45]. The molecular structures of the hit compounds TD12 , TD18 and TD34 are shown in Figure 6B.…”

Section: Resultssupporting

confidence: 75%

Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening

et al. 2019

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Cancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine patients’ immune systems, leading to poor disease outcomes. Both enzymes are validated targets for cancer immunotherapy but there is a paucity of potent TDO2 and dual IDO1/TDO2 inhibitors. To identify novel dual IDO1/TDO2 scaffolds, 3D shape similarity and pharmacophore in silico screening was conducted using TDO2 as a model for both systems. The obtained hits were tested in cancer cell lines expressing mainly IDO1 (SKOV3—ovarian), predominantly TDO2 (A172—brain), and both IDO1 and TDO2 (BT549—breast). Three virtual screening hits were confirmed as inhibitors (TD12, TD18 and TD34). Dose response experiments showed that TD34 is the most potent inhibitor capable of blocking both IDO1 and TDO2 activity, with the IC50 value for BT549 at 3.42 µM. This work identified new scaffolds able to inhibit both IDO1 and TDO2, thus enriching the collection of dual IDO1/TDO2 inhibitors and providing chemical matter for potential development into future anticancer drugs.

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Section: Resultssupporting

confidence: 75%

Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening

et al. 2019

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“…Cui et al 80 isolated and identified ethylnaphthoquinone derivatives in the mangrove endophytic fungus N. austral SYSU-SKS024. It was the first time to discover a novel inhibiting IDO carbon skeleton that showed a good effect.…”

Section: The Inhibitors Of Ido or Tdo In Treatmentmentioning

confidence: 99%

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Ye¹,

Yue²,

Shi³

et al. 2019

J. Cancer

151

111

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Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.

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“…[91]. Bioassay-guided fractionation of the dichloromethane extract of the fungus Neofusicoccum austral SYSU-SKS024 led to the isolation of three new ethylnaphthoquinone derivatives, neofusnaphthoquinone A 284 (Figure 10), 6-(1-methoxylethy1)-2,7-dimethoxyjuglone 285 (Figure 10), (3R,4R)-3-methoxyl-botryosphaerone D 286 (Figure 10), Neofusnaphthoquinone A 285 is the third example of the unsymmetrical naphthoquinone [92]. The EtOAc extract of strain Nectria pseudotrichia 120-1NP led to the identification of one new naph-thoquinone, namely, nectriaquinone B 287 (Figure 10) [31].…”

Section: Anthraquinonesmentioning

confidence: 99%

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

Zheng

Zhang

et al. 2021

IJMS

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Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.

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Ethylnaphthoquinone derivatives as inhibitors of indoleamine-2, 3-dioxygenase from the mangrove endophytic fungus Neofusicoccum austral SYSU-SKS024

Cited by 17 publications

References 24 publications

Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening

Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening

Role of IDO and TDO in Cancers and Related Diseases and the Therapeutic Implications

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

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