Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors

Botić, Tanja; Defant, Andrea; Zanini, Pietro; Žužek, Monika C.; Frangež, Robert; Janussen, Dorte; Kersken, Daniel; Knez, Željko; Mancini, Ines; Sepčić, Kristina

doi:10.1016/j.ejmech.2017.05.019

Cited by 33 publications

(33 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…481 A joint HR-ESI-MS study in conjunction with data mining of published bioactivity data has allowed a comprehensive analysis of the SAR related to the discorhabdin alkaloid family to predict the most important components of the pharmacophore; 482 additionally several discorhabdin congeners have been shown to be reversible inhibitors of various cholinesterases and hence may have potential as treatments for Alzheimer's disease. 483 The treatment of pain and epilepsy are potential outcomes from the discovery that oroidin-type alkaloids are modulators of the K v 1 subfamily of voltage gated potassium ion channels. 484 The merosesquiterpenoid metachromin A has been found to have nanomolar antiviral activity against hepatitis B via impairment of viral promoter activity, 485 while several furanoditerpenoids are new protein tyrosine phosphatase 1B inhibitors.…”

Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2019

View full text Add to dashboard Cite

show abstract

“…While results are still scarce emerging evidence indicates that North-Atlantic (Jackson et al, 2013;Kennedy et al, 2014) or Antarctic (Webster et al, 2004;Xin et al, 2011;Rodríguez-Marconi et al, 2015) cold-and/or deep-water sponges harbor diverse prokaryotic communities. Moreover, deep-sea sponges from the Atlantic exhibited novel secondary metabolite synthetic gene clusters of potential prokaryotic origin (Borchert et al, 2016), and Antarctic deep-water sponges proved to be rich sources of bioactive natural compounds (Turk et al, 2013;Berne et al, 2016;Botić et al, 2017;Angulo-Preckler et al, 2018;Mangano et al, 2018). Consequently, further studies on sponge-microbe associations from rarely accessed environments, such as the Antarctic shelf have the potential to lead to the discovery of novel metabolic mechanisms and bioactive natural compounds for a vast range of biotechnological applications (Sipkema, 2016).…”

Section: Introductionmentioning

confidence: 99%

Prokaryotic Diversity and Community Patterns in Antarctic Continental Shelf Sponges

et al. 2019

Self Cite

View full text Add to dashboard Cite

Marine sponges (Phylum Porifera) are globally distributed within marine and freshwater ecosystems. In addition, sponges host dense and diverse prokaryotic communities, which are potential sources of novel bioactive metabolites and other complex compounds. Those sponge-derived natural products can span a broad spectrum of bioactivities, from antibacterial and antifungal to antitumor and antiviral compounds. However, most analyses concerning sponge-associated prokaryotes have mainly focused on conveniently accessible relatively shallow sampling locations for sponges. Hence, knowledge of community composition, host-relatedness and biotechnological potential of prokaryotic associations in temperate and cold-water sponges from greater depths (mesophotic to mesopelagic zones) is still scarce. Therefore, we analyzed the prokaryotic community diversity of four phylogenetically divergent sponge taxa from mesophotic to mesopelagic depths of Antarctic shelf at different depths and locations in the region of the South Shetland Islands using 16S rRNA gene ampliconbased sequencing. In addition, we predicted functional profiles applying Tax4Fun from metagenomic 16S rRNA gene data to estimate their biotechnological capability and possible roles as sources of novel bioactive compounds. We found indications that cold and deep-water sponges exhibit host-specific prokaryotic communities, despite different sampling sites and depths. Functional prediction analysis suggests that the associated prokaryotes may enhance the roles of sponges in biodegradation processes of xenobiotics and their involvement in the biosynthesis of secondary metabolites.

show abstract

“…Molecular docking has been the major SB methodology to predict affinities to macromolecular targets, to interpret binding modes, and to assist in the design of drug leads. Several recent publications illustrate the application of the method to MNPs [ 127 , 128 , 129 , 138 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ], and some representative examples are here described.…”

Section: Computer-aided Drug Design (Cadd)mentioning

confidence: 99%

Computational Methodologies in the Exploration of Marine Natural Product Leads

Pereira

Aires-de-Sousa

2018

Marine Drugs

View full text Add to dashboard Cite

Computational methodologies are assisting the exploration of marine natural products (MNPs) to make the discovery of new leads more efficient, to repurpose known MNPs, to target new metabolites on the basis of genome analysis, to reveal mechanisms of action, and to optimize leads. In silico efforts in drug discovery of NPs have mainly focused on two tasks: dereplication and prediction of bioactivities. The exploration of new chemical spaces and the application of predicted spectral data must be included in new approaches to select species, extracts, and growth conditions with maximum probabilities of medicinal chemistry novelty. In this review, the most relevant current computational dereplication methodologies are highlighted. Structure-based (SB) and ligand-based (LB) chemoinformatics approaches have become essential tools for the virtual screening of NPs either in small datasets of isolated compounds or in large-scale databases. The most common LB techniques include Quantitative Structure–Activity Relationships (QSAR), estimation of drug likeness, prediction of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, similarity searching, and pharmacophore identification. Analogously, molecular dynamics, docking and binding cavity analysis have been used in SB approaches. Their significance and achievements are the main focus of this review.

show abstract

Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors

Cited by 33 publications

References 40 publications

Marine natural products

Marine natural products

Prokaryotic Diversity and Community Patterns in Antarctic Continental Shelf Sponges

Computational Methodologies in the Exploration of Marine Natural Product Leads

Contact Info

Product

Resources

About