The effect of the isomers of cyclo(Trp-Pro) on heart and ion-channel activity

Jamie, H; Kilian, Gareth; Dyason, Karin; Milne, P. J.

doi:10.1211/002235702252

Cited by 14 publications

(9 citation statements)

References 19 publications

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“…Many investigations reveal DKPs to be antitumour, antibacterial and antifungal agents (Prasad, 1995;Milne et al 1998;Strö m et al 2002;McCleland et al 2004). For instance, cyclo-(Trp-Pro) has been therapeutically used in the modulation of membrane potassium ion channels (Jamie et al 2002). However, the present study is the first to show the antifouling activity of these compounds.…”

Section: Discussionmentioning

confidence: 62%

Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus

et al. 2006

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Modern antifouling coatings use heavy metals and toxic organic molecules to prevent biofouling, the undesirable growth of marine organisms on man-made substrata. In an ongoing survey of deep-sea microorganisms aimed at finding low toxic antifouling metabolites, an actinomycete bacterium was isolated from the Pacific sediment at the depth of about 5000 m. The bacterium was closely related to Streptomyces fungicidicus (99% similarity) according to 16S ribosomal RNA sequence information. The spent culture medium of this bacterium inhibited barnacle larval attachment. Bioassay-guided fractionation was employed to isolate antifouling compounds. The ethyl acetate extract was fractionated by using an open silica gel column. Active fractions were further purified on a HPLC C 18 column., and cyclo-(L-Leu-L-Val) were isolated for the first time from a deep sea bacterium, and the structures of the compounds were elucidated by nuclear magnetic resonance spectroscopy and mass spectrometry. The pure diketopiperazines were tested for antilarval activity using the barnacle Balanus amphitrite. Effective concentrations that inhibited 50% larval attachment (EC 50 ) after 24 h ranged from 0.10 -0.27 mM. The data suggest that diketopiperazines and other compounds from deep-sea bacteria may be used as novel antifoulants.

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Section: Discussionmentioning

confidence: 62%

Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus

et al. 2006

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“…Tryptophan derivatives like the DKPs identified are especially interesting for presenting an indole moiety, which is common in medicinal chemistry and may influence several biological activities [51,52]. Brevianamide F is also reported as a potential compound for treatment of cardiovascular dysfunction [53]. As shown, fatty amides, XA and DKPs were mainly produced in A1 and PC-1 media.…”

Section: Plos Onementioning

confidence: 80%

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

et al. 2020

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Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds.

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“…3C, left panel). Even complete absence of changes in the QRS-complex width under the effect of a drug blocking I Na has been documented, for example under the effect of mexiletine (Shimizu et al 2000) and cyclo(Trp-Pro) isomers (Jamie et al 2002). These differences between results of in vivo and in vitro experiments may be caused, among others (e.g.…”

Section: Discussionmentioning

confidence: 99%

Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers

Kilianová

Bébarová

Beránková³

et al. 2010

Acta Vet. Brno

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Two newly synthesized short-acting agents 44Bu and 444 were observed to suppress the aconitine-induced arrhythmias and block the fast sodium current I Na in the rat heart. No data about their effect on the electrocardiographic parameters are available. In this study, we explored the effect of both racemates and particular isomers of 44Bu and 444 on the QRS-complex width in vivo in rats and on I Na in isolated rat ventricular myocytes. All variants of 44Bu and 444 (1.5 mg/kg) caused a significant QRS-widening reaching the peak effect at the 1 st or 2 nd min after their intravenous administration. 44Bu racemate widened the QRS-complex from 16.8 ± 0.4 to 26.3 ± 0.5 ms (by 57%), significantly more than R-(33%-widening) and S-isomer (36%-widening). 444 racemate widened the QRS-complex from 20.8 ± 1.0 to 34.1 ± 0.9 ms (by 64%), which was comparable to S-isomer (63%-widening), however, substantially more than R-isomer (40%-widening). Regarding the effect on I Na , 44Bu caused a significantly deeper I Nablock compared to 444 when applied at the same concentration of 3 µmol/l (0.1 mg/kg). 44Bu racemate and R-isomer blocked I Na similarly (91.7 ± 0.8 and 91.8 ± 1.6%-block, respectively) and significantly more than S-isomer (82.4 ± 2.3%-block). 444 R-isomer blocked I Na less than racemate and S-isomer (by 31.7 ± 3.9% vs. 48.3 ± 4.7 and 50.2 ± 4.1%, respectively). We conclude that both racemates and particular isomers of 44Bu and 444 induce a QRS-widening and block I Na in the rat heart, however, their effects notably differed. The relative widening of the QRS-complex after application of 44Bu did not conform to the level of I Na -block observed in isolated cardiomyocytes which stresses the importance of in vivo experiments in the pre-clinical testing of new drugs.

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The effect of the isomers of cyclo(Trp-Pro) on heart and ion-channel activity

Cited by 14 publications

References 19 publications

Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus

Antifouling diketopiperazines produced by a deep-sea bacterium,Streptomyces fungicidicus

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds

Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers

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