Inhibition of biofilm formation by conformationally constrained indole-based analogues of the marine alkaloid oroidin

Hodnik, Žiga; Łoś, Jerzy; Žula, Aleš; Zidar, Nace; Łoś, Marcin; Dolenc, Marija Sollner; Ilaš, Janez; Węgrzyn, Grzegorz; Mašič, Lucíja Peterlin; Kikelj, D.

doi:10.1016/j.bmcl.2014.03.094

Cited by 26 publications

(18 citation statements)

References 31 publications

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“…Dihydrosventrin and sventrin, bromopyrrole alkaloids, isolated from marine sponges, are biofilm inhibitors at 51 and 74 µM against P. aeruginosa [10]. The 2-aminoimidazole oroidin, a marine alkaloid, isolated from the marine sponge Agelas conifer , and its analogues are studied for antibiofilm activity [11]. Sortase A (SrtA), a transpeptidase involved in the anchoring of surface proteins to the Gram-positive bacterial cell wall, plays a key role in bacterial adhesion, immune evasion and biofilm formation [12,13].…”

Section: Introductionmentioning

confidence: 99%

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

et al. 2018

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New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form.

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Section: Introductionmentioning

confidence: 99%

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

et al. 2018

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“…We have recently designed several structural classes of analogues of marine alkaloids based on clathrodin, hymenidin and oroidin, isolated from sponges of the genus Agelas, and evaluated their voltage-gated sodium channel modulatory activity [26][27][28][29], inhibition of biofilm formation [30], antimicrobial activity [31], and pro-apoptotic activity in HepG2 and THP-1 cell lines [32]. The similarity of oroidin and its analogues to the known pyrrolamide-based inhibitors [17,18] stimulated us to evaluate selected oroidin analogues from our library for E. coli DNA gyrase inhibition.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors

Tomašič

Mirt

Barančoková

et al. 2017

Bioorganic & Medicinal Chemistry

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Development of novel DNA gyrase B inhibitors is an important field of antibacterial drug discovery whose aim is to introduce a more effective representative of this mechanistic class into the clinic. In the present study, two new series of Escherichia coli DNA gyrase inhibitors bearing the 4,5-dibromopyrrolamide moiety have been designed and synthesized. 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazole-2,6-diamine derivatives inhibited E. coli DNA gyrase in the submicromolar to low micromolar range (IC values between 0.891 and 10.4μM). Their "ring-opened" analogues, based on the 2-(2-aminothiazol-4-yl)acetic acid scaffold, displayed weaker DNA gyrase inhibition with IC values between 15.9 and 169μM. Molecular docking experiments were conducted to study the binding modes of inhibitors.

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“…As a part of this crusade, we have focused on enhancing the antibiofilm properties of promising 2-aminoimidazole (2AI) derivatives[5, 16, 18-20]. One particular class of these 2AI molecules, referred to as the reverse-amides or RA-2AIs (named for the ‘flipped’ orientation of the amide linkage used to synthesize this family of derivatives from the original parent molecule, oroidin[21]) not only efficiently inhibit A. baumannii biofilm formation but also disperse previously formed biofilms[21-22].…”

Section: Introductionmentioning

confidence: 99%

Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii

Stowe¹,

Thompson²,

Peng³

et al. 2015

CDD

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Acinetobacter baumannii has quickly become one of the most insidious and prevalent nosocomial infections. Recently, the reverse-amide class of 2-aminoimidazole compounds (RA-2AI) was found both to prevent A. baumannii biofilm formation and also to disperse preexisting formations, putatively through interactions with cytosolic response regulators. Here we focus on how this class of antibiofilm agent traverses cellular membranes. Following the discovery of dosage-dependent growth rate changes, the cellular effects of RA-2AI were investigated using a combination of molecular assays and microscopic techniques. It was found that RA-2AI exposure has measureable effects on the bacterial membranes, resulting in a period of increased permeability and visible structural aberrations. Based on these results, we propose a model that describes how the structure of RA-2AI allows it to insert itself into and disrupt the fluidity of the membrane, creating an opportunity for increased molecular permeability.

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Inhibition of biofilm formation by conformationally constrained indole-based analogues of the marine alkaloid oroidin

Cited by 26 publications

References 31 publications

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors

Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii

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