Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer’s Disease: A Computational Study

Llorach-Parés, Laura; Nonell-Canals, Alfons; Ávila, Conxita; Sánchez-Martínez, Melchor

doi:10.3390/md16100386

Cited by 31 publications

(17 citation statements)

References 103 publications

(177 reference statements)

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“…These HBs are established with residues F67, V70, K85, D133, V135, R141, Q185, C199 and D200. Most of the listed aminoacidic residues are configuring the ATP binding pocket ( Figure 4B) [16,29,30,72]. For the substrate binding pocket, we found sixteen important HBs.…”

Section: Binding Of Meridianins and Lignarenone B To The Atp And Subsmentioning

confidence: 88%

“…The modelled protein structures and the marine molecules were employed as input of the calculations executed over each of the two cavities using Itzamna software tool [51]. More details on this approach can be found in the literature [29,30].…”

Section: Docking Calculationsmentioning

confidence: 99%

“…Marine natural products, comprising a huge variety of chemical structures and being a serendipitous source of new molecules, could play a key role on this need [26][27][28][29][30][31]. In fact, the biomedical and pharmacological potential of marine natural products is known to be still underexplored [32,33].…”

Section: Introductionmentioning

confidence: 99%

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Meridianins and Lignarenone B as Potential GSK3β Inhibitors and Inductors of Structural Neuronal Plasticity

et al. 2020

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Glycogen Synthase Kinase 3 (GSK3) is an essential protein, with a relevant role in many diseases such as diabetes, cancer and neurodegenerative disorders. Particularly, the isoform GSK3β is related to pathologies such as Alzheimer's disease (AD). This enzyme constitutes a very interesting target for the discovery and/or design of new therapeutic agents against AD due to its relation to the hyperphosphorylation of the microtubule-associated protein tau (MAPT), and therefore, its contribution to neurofibrillary tangles (NFT) formation. An in silico target profiling study identified two marine molecular families, the indole alkaloids meridianins from the tunicate genus Aplidium, and lignarenones, the secondary metabolites of the shelled cephalaspidean mollusc Scaphander lignarius, as possible GSK3β inhibitors. The analysis of the surface of GSK3β, aimed to find possible binding regions, and the subsequent in silico binding studies revealed that both marine molecular families can act over the ATP and/or substrate binding regions. The predicted inhibitory potential of the molecules from these two chemical families was experimentally validated in vitro by showing ã 50% of increased Ser9 phosphorylation levels of the GSK3β protein. Furthermore, we determined that molecules from both molecular families potentiate structural neuronal plasticity in vitro. These results allow us to suggest that meridianins and lignarenone B could be used as possible therapeutic candidates for the treatment of GSK3β involved pathologies, such as AD.

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Section: Binding Of Meridianins and Lignarenone B To The Atp And Subsmentioning

confidence: 88%

Section: Docking Calculationsmentioning

confidence: 99%

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Meridianins and Lignarenone B as Potential GSK3β Inhibitors and Inductors of Structural Neuronal Plasticity

et al. 2020

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“…Kororamides A and B (11a-11b, Figure 11) are tribrominated indolic derivatives isolated from the bryozoan Amathia tortuosa [170,171]. A computational study on kororamides as well as on convolutamines (7, Figure 8) suggested they could act as tau and dual-specificity kinase inhibitors for Alzheimer's disease [172].…”

Section: Alzheimer's Disease (Ad)mentioning

confidence: 99%

The Phylum Bryozoa: From Biology to Biomedical Potential

et al. 2020

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Less than one percent of marine natural products characterized since 1963 have been obtained from the phylum Bryozoa which, therefore, still represents a huge reservoir for the discovery of bioactive metabolites with its ~6000 described species. The current review is designed to highlight how bryozoans use sophisticated chemical defenses against their numerous predators and competitors, and which can be harbored for medicinal uses. This review collates all currently available chemoecological data about bryozoans and lists potential applications/benefits for human health. The core of the current review relates to the potential of bryozoan metabolites in human diseases with particular attention to viral, brain, and parasitic diseases. It additionally weighs the pros and cons of total syntheses of some bryozoan metabolites versus the synthesis of non-natural analogues, and explores the hopes put into the development of biotechnological approaches to provide sustainable amounts of bryozoan metabolites without harming the natural environment.

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“…Convolutamine F also displayed inhibitory effect for cell division of fertilized sea urchin eggs [46]. Convolutamines I-J, isolated from the Southern Ocean bryozoan A. tortuosa Tenison-Woods, 1880, were recently validated as potential ATP competitive inhibitors [47]. Lutamides A and C exhibited inhibition against adriamycin (ADM)-resistant P388/ADM, vincristine (VCR)-resistant P388/VCR and KB/VJ300 cells in the presence of ADM or VCR whose concentration did not affect growth of the cells examined [44].…”

Section: Convolutamides Convolutamydines and Convolutaminesmentioning

confidence: 99%

The Understudied Phylum Bryozoa as a Promising Source of Anticancer Drugs

Figuerola¹,

Ávila²

2019

Preprint

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Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, filter-feeding, sessile aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which is advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumour compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.

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Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer’s Disease: A Computational Study

Cited by 31 publications

References 103 publications

Meridianins and Lignarenone B as Potential GSK3β Inhibitors and Inductors of Structural Neuronal Plasticity

Meridianins and Lignarenone B as Potential GSK3β Inhibitors and Inductors of Structural Neuronal Plasticity

The Phylum Bryozoa: From Biology to Biomedical Potential

The Understudied Phylum Bryozoa as a Promising Source of Anticancer Drugs

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