Structure–anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives

Sawada, Hiromi; Onoda, Kenji; Morita, Daichi; Ishitsubo, Erika; Matsuno, Kenji; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki

doi:10.1016/j.bmcl.2013.10.069

Cited by 13 publications

(16 citation statements)

References 15 publications

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“…From its chemical structure, riccardin C derivatives would be different from these ionophores. We previously showed the obvious structure-activity relationship of riccardin C derivatives [6,7]. This fact reminds us that riccardin C derivatives may bind to a peculiar target molecule on the membrane, not at random.…”

Section: Discussionmentioning

confidence: 90%

“…RC-112, AA-99, and AA-100 exhibited strong anti-MRSA activities (Table 1) [6,7]. When RC-112 was added at the concentration of the MIC, the number of viable cells was not decreased or significantly different from that of the control (no addition).…”

Section: Effect Of the Riccardin C Derivatives On Survival Of S Aureusmentioning

confidence: 89%

“…Therefore, RC-112 derivatives may have dual targets for their antimicrobial activities. We recently reported the chemical synthesis of novel RC-112 derivatives and their anti-MRSA activities [6,7]. Further analyses of these derivatives are required to elucidate their structure-activity relationships and mechanisms of membrane damage in more detail.…”

Section: Discussionmentioning

confidence: 99%

“…1) [6,7]. To investigate the action mechanism of riccardin C derivatives, we first performed a survival assay for S. aureus N315.…”

Section: Effect Of the Riccardin C Derivatives On Survival Of S Aureusmentioning

confidence: 99%

“…We previously reported that riccardin C exhibited anti-MRSA activity [6,7]. Riccardin C, a macrocyclic bis (bibenzyl) compound, was originally discovered in liverworts [8], and exhibits cyclooxygenase (COX)-inhibitory [9], HIV-1 reverse transcriptase-inhibitory [10], antifungal [10], the nuclear receptor family transcription factors Liver X Receptor (LXR)-modulating [11], and anti-cancer [12] activities.…”

Section: Introductionmentioning

confidence: 99%

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Riccardin C derivatives cause cell leakage in Staphylococcus aureus

Morita

Sawada

Ogawa

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in clinical settings, and because it is resistant to most antimicrobial agents, MRSA infections are difficult to treat. We previously reported that synthetic macrocyclic bis(bibenzyl) derivatives, which were originally discovered in liverworts, had anti-MRSA activity. However, the action mechanism responsible was unclear. In the present study, we elucidated the action mechanism of macrocyclic bis(bibenzyl) RC-112 and its partial structure, IDPO-9 (2-phenoxyphenol). Survival experiments demonstrated that RC-112 had a bactericidal effect on MRSA, whereas IDPO-9 had bacteriostatic effects. IDPO-9-resistant mutants exhibited cross-resistance to triclosan, but not to RC-112. The mutation was identified in the fabI, enoyl-acyl carrier protein reductase gene, a target of triclosan. We have not yet isolated the RC-112-resistant mutant. On the other hand, the addition of RC-112, unlike IDPO-9, caused the inflow of ethidium and propidium into S. aureus cells. RC-112-dependent ethidium outflow was observed in ethidium-loaded S. aureus cells. Transmission electron microscopy also revealed that S. aureus cells treated with RC-112 had intracellular lamellar mesosomal-like structures. Intracellular Na+ and K+ concentrations were significantly changed by the RC-112 treatment. These results indicated that RC-112 increased membrane permeability to ethidium, propidium, Na+, and K+, and also that the action mechanism of IDPO-9 was different from those of the other compounds.

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Section: Discussionmentioning

confidence: 90%

Section: Effect Of the Riccardin C Derivatives On Survival Of S Aureusmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

“…1) [6,7]. To investigate the action mechanism of riccardin C derivatives, we first performed a survival assay for S. aureus N315.…”

Section: Effect Of the Riccardin C Derivatives On Survival Of S Aureusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Riccardin C derivatives cause cell leakage in Staphylococcus aureus

Morita

Sawada

Ogawa

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Macrocyclic Olefin Metathesis at High Concentrations by Using a Phase‐Separation Strategy

Raymond¹,

Holtz-Mulholland²,

Collins³

2014

Chemistry A European J

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Macrocyclic olefin metathesis has seen advances in the areas of stereochemistry, chemoselectivity, and catalyst stability, but strategies aimed at controlling dilution effects in macrocyclizations are rare. Herein, a protocol to promote macrocyclic olefin metathesis, one of the most common synthetic tools used to prepare macrocycles, at relatively high concentrations (up to 60 mM) is described by exploitation of a phase-separation strategy. A variety of macrocyclic skeletons could be prepared having either different alkyl, aryl, or amino acids spacers.

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One‐Pot Tandem Coupling Method for the Short‐Step Formal Synthesis of Riccardin C

Kobatake

Miyoshi

Ueno

2023

Chemistry A European J

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One-pot reactions reduce reagent amounts and circumvent process treatments, such as work-up and purifications in multi-step reactions. In this study, we achieved the formal total synthesis of riccardin C through a one-pot reaction by simultaneously linking four units through two Sonogashira coupling reactions and one Suzuki coupling reaction, followed by reduction and deprotection. Thus, this one-pot method comprised five steps and did not require the purification of intermediate reaction mixtures, which saves resources, such as reagents and solvents, and expedites the work process.

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Structure–anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives

Cited by 13 publications

References 15 publications

Riccardin C derivatives cause cell leakage in Staphylococcus aureus

Riccardin C derivatives cause cell leakage in Staphylococcus aureus

Macrocyclic Olefin Metathesis at High Concentrations by Using a Phase‐Separation Strategy

One‐Pot Tandem Coupling Method for the Short‐Step Formal Synthesis of Riccardin C

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