Functionalized resorcinarenes effectively disrupt the aggregation of αA66-80 crystallin peptide related to cataracts

Twum, Kwaku; Bhattacharjee, Avik; Laryea, Erving T.; Esposto, Josephine; Omolloh, George; Mortensen, Shaelyn; Jaradi, Maya; Stock, Naomi L.; Schileru, Nicholas; Elias, Bianca; Pszenica, Elan; McCormick, Theresa M.; Martić, Sanela; Beyeh, Ngong Kodiah

doi:10.1039/d1md00294e

Cited by 7 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The symptoms of early cataract are not obvious, and the main treatment methods include surgical resection and drug therapy (Bhalerao et al, 2021;Zhang et al, 2017). Although the majority of cases can achieve good results, the effect of drug therapy is limited because of unclear pathogenesis (Twum et al, 2021;Yin et al, 2017). In this study, we found that ORI increased cell viability of H 2 O 2 -indued cells, reduced cell apoptosis, and alleviated oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Chen

Zeng

Xiao

et al. 2023

Qual. Assur. Saf. Crops Foods

View full text Add to dashboard Cite

Cataract is the clouding of eye lens, and is the leading cause of visual impairment and blindness worldwide. There is an urgent need to develop new drugs to combat this disease. Oridonin (ORI), isolated from Rabdosia rubescens, is a natural substance that has been studied as an activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and covalent inhibitor of NLR family pyrin domain containing 3 (NLRP3). Whether ORI has a therapeutic effect on human lens’ epithelial cell injury needs further study. In this study, we used cataract lens epithelial cell lines HLE-B3 and SRA01/04. We found using the MTT assay that ORI treatment increased cell viability induced by hydrogen peroxide (H2O2). In addition, ORI suppressed the apoptosis of H2O2-induced HLE-B3 and SRA01/04 cells detected by flow cytometry and Western blot analysis. Our data further revealed that ORI regulated nuclear factor, erythroid 2 (NFE2) like bZIP transcription factor 2 (Nrf2)-mediated oxidative stress by enzyme-linked-immunosorbent serologic assay. We further found that ORI inhibited NLRP3/nuclear factor-κb (NF-κB) pathway in H2O2-induced HLE-B3 and SRA01/04 cells by Western blot analysis. Therefore, these results suggested that ORI could have the potential to serve as a promising drug to treat cataract.

show abstract

Section: Discussionmentioning

confidence: 99%

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Chen

Zeng

Xiao

et al. 2023

Qual. Assur. Saf. Crops Foods

View full text Add to dashboard Cite

show abstract

“…Calixarenes, resorcinarenes, and other macrocyclic cavitands are widely studied hosts for many guest systems [1–4] . These hosts are known for their ability to bind molecular guests through multiple non‐covalent interactions in their tailored but shallow internal cavities [5] .…”

Section: Introductionmentioning

confidence: 99%

“…Calixarenes, resorcinarenes, and other macrocyclic cavitands are widely studied hosts for many guest systems. [1][2][3][4] These hosts are known for their ability to bind molecular guests through multiple non-covalent interactions in their tailored but shallow internal cavities. [5] Amongst many architectures reported, twocomponent dimeric and hexameric capsules are relatively common [6,7] while all organic three-component assemblies are relatively rare.…”

Section: Introductionmentioning

confidence: 99%

The “Nitrogen Effect”: Complexation with Macrocycles Potentiates Fused Heterocycles to Form Halogen Bonds in Competitive Solvents

Twum

Nadimi

Osei

et al. 2023

Chemistry An Asian Journal

Self Cite

View full text Add to dashboard Cite

Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three‐component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N‐heterocycles in an open resorcinarene cavity to template the formation of a three‐component halogen‐bonded ternary assembly in a protic polar solvent system.

show abstract

“…Resorcinarenes (Figure ) are a class of cyclic polyphenolic compounds obtained by the condensation of resorcinol with different aldehydes in acidic solutions. Interestingly, owing to the flexibility in changing the electron-rich upper-rim groups and lower-rim alkyl chains with distinctive substituents, a wide assortment of tunable host molecules can be obtained. , For instance, water-soluble anionic and cationic resorcinarene receptors disrupt the aggregation of the peptide associated with cataracts, which highlights the potential of tunable resorcinarenes in therapeutics. Among cyclic polyphenolic cavitands, resorcinarenes have been studied extensively in host–guest chemistry, as their conical shape has the potential for the development of useful (bio)materials and sensors .…”

mentioning

confidence: 99%

Supramolecule-Driven Host–Guest Co-Crystallization of Cyclic Polyphenols with Anti-Fibrotic Pharmaceutical Drug

Panigrahi

Mayhan

Dar

et al. 2023

Crystal Growth & Design

View full text Add to dashboard Cite

Host–guest complexes are of interest as supramolecular drugs in pharmaceutical sciences because the activity of antibacterial agents can be enhanced upon complexation with various cyclic oligomers or metal ions, with some complexes possessing higher healing properties than the parent drugs. Herein, to develop a microbiologically potent supramolecular drug, we investigated the complexation of macrocyclic hosts (resorcinarenes and β-cyclodextrin) with pirfenidone (PFD), an FDA-approved antifibrotic drug containing an antibacterial pyridone core. Electronic structure calculations gave insights into the interactions in the host–PFD complexes. Further, complex formation and clinical activities were investigated using spectroscopic techniques and in vitro measurements of antibacterial activity against Gram-positive and Gram-negative bacteria. An unprecedented interplay between the antibacterial activity of the polyphenolic resorcinarene hosts and their ability to interact chemically with PFD was found to improve the overall antibacterial activity of PFD. These results could revolutionize the use of synthetically modifiable resorcinarene and their analogues for fine-tuning the clinical behavior of drugs.

show abstract

Functionalized resorcinarenes effectively disrupt the aggregation of αA66-80 crystallin peptide related to cataracts

Abstract: Ionic resorcinarenes successfully disrupt the aggregation of αA66-80 crystallin peptide related to cataracts. The results show functionalized resorcinarenes as potential agents to reverse the aggregation of α-crystallin dominant in eye cataracts.

Cited by 7 publications

References 37 publications

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

The “Nitrogen Effect”: Complexation with Macrocycles Potentiates Fused Heterocycles to Form Halogen Bonds in Competitive Solvents

Supramolecule-Driven Host–Guest Co-Crystallization of Cyclic Polyphenols with Anti-Fibrotic Pharmaceutical Drug

Contact Info

Product

Resources

About