Evaluation of Flavonoid and Resveratrol Chemical Libraries Reveals Abyssinone II as a Promising Antibacterial Lead

Sun, Dianqing; Hurdle, Julian G.; Lee, Robin E.; Lee, Richard; Cushman, Mark; Pezzuto, John M.

doi:10.1002/cmdc.201200253

Cited by 37 publications

(39 citation statements)

References 75 publications

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“…30, 31 Briefly, cells were mixed with tested compound for 5 min before the addition of precursors at 1 μCi ml −1 . After an additional 20 min, cells were lysed with cold 10% TCA and precipitated macromolecules collected on GF/C filters.…”

Section: Methodsmentioning

confidence: 99%

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Shen¹,

Maddox²,

Adhikari³

et al. 2013

J Antibiot

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The natural product engelhardione is an underexplored chemotype for developing novel treatments for bacterial infections; we therefore explored this natural product scaffold for chemical diversification and structure-activity relationship studies. Macrocyclic engelhardione and structural regioisomers were synthesized using a series of aldol condensations and selective hydrogenations to generate the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether analogs. An extended macrocyclic chemical library was then produced by oxime formation, reductive amination, and O-alkylation. Antibacterial evaluation revealed that the reductive amination derivatives 7b and 7d showed moderate activities (minimum inhibitory concentrations: 12.5-25 μg ml−1) against Mycobacterium tuberculosis and Gram-positive pathogens, as well as anti-Gram-negative activity against an efflux impaired E. coli strain. These results provide validated leads for further optimization and development.

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Section: Methodsmentioning

confidence: 99%

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Shen¹,

Maddox²,

Adhikari³

et al. 2013

J Antibiot

Self Cite

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“…Emerging evidence has shown that prenylated flavonoids could protect plants against diseases by strongly inhibiting bacterial and fungal activities (Inui et al, 2012;Morel et al, 2012;Mukne et al, 2011;Ruddock et al, 2011;Sasaki et al, 2012;Shen et al, 2012;Sun et al, 2012;Sutthivaiyakit et al, 2009). There was some evidence suggesting that prenylation increased the lipophilicity of flavonoids, which resulted in an increased affinity to biological membranes and an improved interaction with target proteins (Hatano et al, 2000).…”

Section: Antibacterial Activitymentioning

confidence: 99%

A systematic review on biological activities of prenylated flavonoids

Chen

Mukwaya

Wong

et al. 2013

Pharmaceutical Biology

190

136

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Context: Prenylated flavonoids are a unique class of naturally occurring flavonoids that exist especially for the plant's self-defensive strategy. This special class of flavonoids increases the bioactivities of their backbone flavonoids with non-prenylation; therefore, prenylated flavonoids have more potential to be developed and utilized. Objective: The number, position and type of the prenyl group on the flavonoids backbone structure may have close relationships with the bioactivities of flavonoids. Methods: PubMed and WEB OF KNOWLEDGEÕ were used to search articles published in English between 1 January 2002 and 31 December 2012, which discuss the structure-activity relationship between prenylated flavonoids and their bioactivities. Results: It is proposed that the prenyl-moiety makes the backbone compound more lipophilic, which leads to its high affinity with cell membranes. The prenylation brings the flavonoids with enhancement of antibacterial, anti-inflammatory, antioxidant, cytotoxicity, larvicidal as well as estrogenic activities. However, it is reported that the prenyl-moiety decreases the bioavailability and plasma absorption of prenylated flavonoids. Conclusion: The prenyl group affects the bioactivities of flavonoids in certain ways, while the action mechanisms and the structure-activity relationship as well as more in vivo studies even clinical validation trials need to be further investigated.

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“…Abyssinone II is one such naturally occurring flavonoid that was recently reported to show moderate antitubercular and anti‐gram‐positive activities against Staphylococcus aureus, Enterococcus faecalis and Streptococcus pneumonia (Sun et al . ). Similarly, olympicin A, isolated from the medicinal plant Hypericum olympicum , showed potent activity against multidrug‐resistant Staph.…”

Section: Introductionmentioning

confidence: 97%

Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection

Alam

Feng

et al. 2013

J Appl Microbiol

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Aims There is a need for novel treatments for Clostridium difficile infection (CDI). Antibacterial flavonoids are part of a large family of polyphenol phytochemicals with a long history of use in ethnomedicine, but are unexamined against C. difficile. We explored their anti-difficile properties. Methods and Results Anti-difficile activities were determined for several naturally occurring flavonoids, olympicin A and synthetic 4-chromanone and chalcone analogs. With the exception of olympicin A, most naturally occurring phytochemicals tested were poorly active. Diversified synthetic flavonoids resembling olympicin A retained anti-difficile activity, suggesting olympicin A could act as a pharmacophore to obtain novel agents. They also demonstrated concentration dependent killing of logarithmic and stationary phase cultures and reduced sporulation and toxin production. Olympicin A and some synthetic flavonoids dissipated the bacterial transmembrane potential. Interestingly, mutants could only be selected with the analog 207 at a frequency of 10-9. Conclusions Based on the potent anti-difficile properties of olympicin A and modified flavonoids, further exploration of this class of phytochemicals is warranted. Significance and Impact of the Study CDI is a major problem in developed countries. These studies point to there being an avenue for optimizing plant-derived flavonoids, and related antibacterial phytochemicals, as nature-inspired approaches to treat CDI.

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Evaluation of Flavonoid and Resveratrol Chemical Libraries Reveals Abyssinone II as a Promising Antibacterial Lead

Cited by 37 publications

References 75 publications

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

A systematic review on biological activities of prenylated flavonoids

Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection

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