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Keywords = clathrodin

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12 pages, 744 KB  
Article
Action of Clathrodin and Analogues on Voltage-Gated Sodium Channels
by Steve Peigneur, Aleš Žula, Nace Zidar, Fiona Chan-Porter, Robert Kirby, David Madge, Janez Ilaš, Danijel Kikelj and Jan Tytgat
Mar. Drugs 2014, 12(4), 2132-2143; https://doi.org/10.3390/md12042132 - 4 Apr 2014
Cited by 10 | Viewed by 7495
Abstract
Clathrodin is a marine alkaloid and believed to be a modulator of voltage-gated sodium (NaV) channels. Since there is an urgent need for small molecule NaV channel ligands as novel therapeutics, clathrodin could represent an interesting lead compound. Therefore, clathrodin [...] Read more.
Clathrodin is a marine alkaloid and believed to be a modulator of voltage-gated sodium (NaV) channels. Since there is an urgent need for small molecule NaV channel ligands as novel therapeutics, clathrodin could represent an interesting lead compound. Therefore, clathrodin was reinvestigated for its potency and NaV channel subtype selectivity. Clathrodin and its synthetic analogues were subjected to screening on a broad range of NaV channel isoforms, both in voltage clamp and patch clamp conditions. Even though clathrodin was not found to exert any activity, some analogues were capable of modulating the NaV channels, hereby validating the pyrrole-2-aminoimidazole alkaloid structure as a core structure for future small molecule-based NaV channel modulators. Full article
(This article belongs to the Special Issue Alkaloid Analogs)
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24 pages, 939 KB  
Article
Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
by Nace Zidar, Sofia Montalvão, Žiga Hodnik, Dorota A. Nawrot, Aleš Žula, Janez Ilaš, Danijel Kikelj, Päivi Tammela and Lucija Peterlin Mašič
Mar. Drugs 2014, 12(2), 940-963; https://doi.org/10.3390/md12020940 - 14 Feb 2014
Cited by 54 | Viewed by 11188
Abstract
Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated [...] Read more.
Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC90 (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound’s potential as an antimicrobial lead, was found to be 2.9 for compound 6h. Full article
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