Physical and virtual screening methods for marine toxins and drug discovery targeting nicotinic acetylcholine receptors

Abstract

Recent years have provided new valuable techniques for the detection and identification of new nAChRs ligands, along with an increasing use of different molecular modeling tools. This furthering of knowledge has had an impact on the design and discovery of more potent and selective nAChRs ligands. There is still however a lack of high-resolution structural information that will require new developments.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…secondary metabolites [268]; marine compounds with therapeutic potential in Gram-negative sepsis [269]; antimicrobial properties of tunichromes [270]; drug discovery from marine microbes [271]; (c) antiviral marine pharmacology : marine natural products with anti-HIV activities in the last decade [272]; fucoidans as potential inhibitors of human immunodeficiency virus type 1 (HIV-1) [273]; discovery of potent broad spectrum antivirals derived from marine Actinobacteria [274]; algal lectins for prevention of HIV transmission [275]; (d) antiprotozoal, antimalarial, antituberculosis and antifungal marine pharmacology : trypanocidal activity of marine natural products [276]; natural sesquiterpenes as lead compounds for the design of trypanocidal drugs [277]; antifungal compounds from marine fungi [278]; (e) immuno- and anti-inflammatory marine pharmacology : immunoregulatory properties of bryostatin [279]; bioactive marine peptides as potential anti-inflammatory therapeutics [280]; anti-inflammatory soft coral marine natural products from Taiwan [281]; marine natural products with potential for the therapeutics of inflammatory diseases [282]; antioxidant properties of crude extracts and compounds from brown marine algae [283]; (f) cardiovascular and antidiabetic marine pharmacology : oxidation of marine omega-3 supplements and human health [284]; marine peptides for prevention of metabolic syndrome [285]; antidiabetic effect of marine brown algae-derived phlorotannins [286]; marine bioactive peptides as potential antioxidants [287]; cardioprotective peptides from marine sources [288]; antioxidant and antidiabetic pharmacology of fucoxantin [289]; marine-derived bioactive peptides as new anticoagulants [290]; (g) nervous system marine pharmacology : marine neurotoxins, structures, molecular targets and pharmacology [291]; the phosphatase inhibitor okadaic acid as a tool to identify phosphoepitopes relevant to neurodegeneration [292]; marine toxins and drug discovery targeting nicotinic acetylcholine receptors [293]; marine-derived marine secondary metabolites and neuroprotection [294]; cone snail polyketides active in neurological assays [295]; and (h) miscellaneous molecular targets and uses : small-molecule inhibitors of clinically validated protein and lipid kinases of marine origin [296]; natural products as kinase inhibitors […”

Molecular Dynamics Simulations Study on the Resistant Mechanism of Insects to Imidacloprid due to Y151‐S and R81T Mutations in nAChRs

“…Over the past decade, Ls‐AChBP has also proven to be a very useful alternative structure to the LBD of nAChRs. The Ls‐AChBP structure was successfully used as a template for homology models of LBD regions of nAChRs, and these models were further developed to study receptor‐ligand interactions and to design new small molecules for nAChRs . In addition, Ls‐AChBP also acts as a substitute for nAChR to study the interaction with small molecules .…”

Spirolides and Cyclic Imines: Toxicological Profile

“…The antagonist activity of 13-desmethyl spirolide C is long-lasting, since it was not annihilated even after a 30-40 min of washout of the spirolide from the nAChR subtypes studied (Bourne et al 2010) (Fig. 4) Molgó et al 2013) allowed to get a better understanding into the interaction between spirolides and nAChRs. These competition-binding assays, performed at equilibrium, demonstrated that 13-desmethyl spirolide C totally displaced [ 125 I]α-bungarotoxin, in a concentration-dependent manner, not only from Torpedo membranes expressing the muscle-type nAChR but also from HEK-293 cells expressing the chicken chimeric α7-5HT 3 neuronal nAChR.…”