Evaluating Marine Cyanobacteria as a Source for CNS Receptor Ligands

Rague, Andrea L; Parker, S J; Tidgewell, Kevin

doi:10.3390/molecules23102665

Cited by 5 publications

(5 citation statements)

References 22 publications

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“…Our initial interest in this compound arose when it was isolated from a cyanobacterial fraction that demonstrated sigma-1 receptor, sigma-2/TMEM97 receptor, DAT, and KOR affinity. Our research has focused on discovering cyanobacterial secondary metabolites with CNS modulatory activity [ 14 , 15 , 16 ]. We used barbamide as a tool to demonstrate the in vitro activity of a cyanobacterial compound on neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons

et al. 2023

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Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.

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Section: Discussionmentioning

confidence: 99%

Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons

et al. 2023

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“…The range of molecules presented in this review is by no means exhaustive, as there are numerous potent cyanobacterial compounds reported in the literature and are beyond the scope of this review. These compounds include the highly cytotoxic compounds, bisebromoamide (65) and aurilide-class of compounds (e.g., 66), antiinfective molecules, almiramides (e.g., 67) and janadolide (68), anti-inflammatory molecule, biseokeaniamide A (69) as well as cannabimimetics/CNS modulatory agents, such as mooreamide A and serinolamides (e.g., 70) (Figure 13) [145][146][147][148][149][150][151][152][153]. Further biological evaluation and synthesis of analogues have also been initiated for some of these compounds [154][155][156][157][158][159].…”

Section: Discussionmentioning

confidence: 99%

Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets

Tan

Phyo

2020

Molecules

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The prokaryotic filamentous marine cyanobacteria are photosynthetic microbes that are found in diverse marine habitats, ranging from epiphytic to endolithic communities. Their successful colonization in nature is largely attributed to genetic diversity as well as the production of ecologically important natural products. These cyanobacterial natural products are also a source of potential drug leads for the development of therapeutic agents used in the treatment of diseases, such as cancer, parasitic infections and inflammation. Major sources of these biomedically important natural compounds are found predominately from marine cyanobacterial orders Oscillatoriales, Nostocales, Chroococcales and Synechococcales. Moreover, technological advances in genomic and metabolomics approaches, such as mass spectrometry and NMR spectroscopy, revealed that marine cyanobacteria are a treasure trove of structurally unique natural products. The high potency of a number of natural products are due to their specific interference with validated drug targets, such as proteasomes, proteases, histone deacetylases, microtubules, actin filaments and membrane receptors/channels. In this review, the chemistry and biology of selected potent cyanobacterial compounds as well as their synthetic analogues are presented based on their molecular targets. These molecules are discussed to reflect current research trends in drug discovery from marine cyanobacterial natural products.

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“…Cyanobacteria inhabit diverse environments and contain rich biosynthetic capacity for formation of diverse molecular structures [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. In 1992, a team at the University of Hawaii reported a novel natural product in a lipophilic extract from the culture containing the cyanobacterium Tolypothrix nodosa [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria

Jin

Zhang

et al. 2021

Life

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Tolyporphins A–R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains Nostoc sp. 106C, Nostoc sp. RF31YmG, Nostoc sp. FACHB-892, Brasilonema octagenarum UFV-OR1, Brasilonema octagenarum UFV-E1, Brasilonema sennae CENA114 and Oculatella sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.

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Evaluating Marine Cyanobacteria as a Source for CNS Receptor Ligands

Cited by 5 publications

References 22 publications

Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons

Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons

Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets

Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria

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