Cladosporamide A, a new protein tyrosine phosphatase 1B inhibitor, produced by an Indonesian marine sponge-derived Cladosporium sp.

Rotinsulu, Henki; Yamazaki, Hiroyuki; Sugai, Shino; Iwakura, Natsuki; Wewengkang, Defny S.; Sumilat, Deiske A.; Namikoshi, Michio

doi:10.1007/s11418-018-1193-y

Cited by 20 publications

(16 citation statements)

References 19 publications

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“…500 marine natural products were obtained from Indonesian sponges from January 1970 to December 2017, while less than 50 compounds were reported from marine fungi during the same period. Furthermore, only a few compounds were isolated from fungal symbionts in Indonesian sponges to date [14,15]. This is strongly indicating that sponge-associated fungi from Indonesia are still underevaluated.…”

Section: Introductionmentioning

confidence: 99%

Two new aromatic polyketides from a sponge-derived Fusarium

Sibero¹,

Zhou²,

Fukaya³

et al. 2019

Beilstein J. Org. Chem.

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In our natural product screening program from marine fungi, two new aromatic polyketides karimunones A (1) and B (2) and five known compounds (3–7) were isolated from sponge-associated Fusarium sp. KJMT.FP.4.3 which was collected from an Indonesian sponge Xestospongia sp. The structures of these compounds were determined by the analysis of NMR and MS spectroscopic data. The NMR assignment of 1 was assisted by DFT-based theoretical chemical shift calculation. Compound 2 showed antibacterial activity against multidrug resistant Salmonella enterica ser. Typhi with a MIC of 125 µg/mL while 1 was not active.

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Section: Introductionmentioning

confidence: 99%

Two new aromatic polyketides from a sponge-derived Fusarium

Sibero¹,

Zhou²,

Fukaya³

et al. 2019

Beilstein J. Org. Chem.

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“…The known (2 S )-7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone ( 59 ) is a prenylated flavanone in which prenylation is represented by 3,3-dimethylallyl substituent at position 8’ [ 93 ].…”

Section: Fifty Years Of Metabolomic Studies In Cladosporiummentioning

confidence: 99%

“…Cladosporactone A ( 74 ), cladosporimide A ( 75 ) and herbaric acid ( 76 ) are lactones isolated for the first time from a marine-derived strain of Cladosporium sp. ( Figure 17 ) [ 35 , 45 , 93 ].…”

Section: Fifty Years Of Metabolomic Studies In Cladosporiummentioning

confidence: 99%

The Genus Cladosporium: A Rich Source of Diverse and Bioactive Natural Compounds

2021

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Fungi are renowned as one of the most fruitful sources of chemodiversity and for their ubiquitous occurrence. Among the many taxonomic groupings considered for the implications deriving from their biosynthetic aptitudes, the genus Cladosporium stands out as one of the most common in indoor environments. A better understanding of the impact of these fungi on human health and activities is clearly based on the improvement of our knowledge of the structural aspects and biological properties of their secondary metabolites, which are reviewed in the present paper.

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“…Compounds 2, 6, 8, and 9 exerted a clearly antihyperglycemic effect since they prevented the hyperglycemic peak at the first hour in a statistically significant manner in contrast to the control group. Phenol and acid natural products isolated from marine sponge and plants have been described in the literature to decrease blood glucose by the inhibition of PTP-1B [29,30]. We focused on the design and synthesis of these acid molecules with antihyperglycemic activity.…”

Section: Antidiabetic Assaymentioning

confidence: 99%

Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect

et al. 2021

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Substituted phenylacetic (1–3), phenylpropanoic (4–6), and benzylidenethiazolidine-2,4-dione (7–9) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements. Addition and substitution reactions were performed to obtain molecules at moderated yields. In silico pharmacological consensus analysis (PHACA) was conducted to determine their possible modes of action, protein affinities, toxicological activities, and drug-like properties. The results were combined with in vivo assays to evaluate the ability of these compounds to decrease glucose levels in diabetic mice at a 100 mg/kg single dose. Compounds 6 (a phenylpropanoic acid derivative) and 9 (a benzylidenethiazolidine-2,4-dione derivative) ameliorated the hyperglycemic peak in a statically significant manner in a mouse model of type 2 diabetes. Finally, molecular dynamics simulations were executed on the top performing compounds to shed light on their mechanism of action. The simulations showed the flexible nature of the binding pocket of AR, and showed that both compounds remained bound during the simulation time, although not sharing the same binding mode. In conclusion, we designed nine acid bioisosteres with robust in vivo antihyperglycemic activity that were predicted to have favorable pharmacokinetic and toxicological profiles. Together, these findings provide evidence that supports the molecular design we employed, where the unified pharmacophores possess a strong antidiabetic action due to their multitarget activation.

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Cladosporamide A, a new protein tyrosine phosphatase 1B inhibitor, produced by an Indonesian marine sponge-derived Cladosporium sp.

Cited by 20 publications

References 19 publications

Two new aromatic polyketides from a sponge-derived Fusarium

Two new aromatic polyketides from a sponge-derived Fusarium

The Genus Cladosporium: A Rich Source of Diverse and Bioactive Natural Compounds

Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect

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