3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, Xiaojuan; Pan, Siyi; Xu, Xiaoyun

doi:10.1038/srep23634

Cited by 75 publications

(60 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, QSAR played an indispensable role in GPCR subtype selective ligand design1415, e.g., ARs16, dopamine receptors17, serotonin receptors 5HT1E/5HT1F18 and cannabinoid receptor CB1/CB21920. For AR ligands, Michelan et al .…”

mentioning

confidence: 99%

Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

Kuang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction.

show abstract

mentioning

confidence: 99%

Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

Kuang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These characteristics favor increased membrane fluidity in the bacterial cell (Tsuchiya and Iinuma, 2000; Wu et al, 2013). In a recent study using a structure-activity relationship model, flavonoids were shown to affect Escherichia coli viability by damaging its outer membrane (Fang et al, 2016). Considering the high hydrophobicity of both flavonoids and the P. aeruginosa cell wall, it is possible that SF32-33 has an effect on P. aeruginosa viability and growth due to a strong hydrophobic interaction.…”

Section: Discussionmentioning

confidence: 99%

Annona glabra Flavonoids Act As Antimicrobials by Binding to Pseudomonas aeruginosa Cell Walls

et al. 2016

View full text Add to dashboard Cite

Pseudomonas aeruginosa is an important pathogen in opportunistic infections in humans. The increased incidence of antimicrobial-resistant P. aeruginosa isolates has highlighted the need for novel and more potent therapies against this microorganism. Annona glabra is known for presenting different compounds with diverse biological activities, such as anti-tumor and immunomodulatory activities. Although other species of the family display antimicrobial actions, this has not yet been reported for A. glabra. Here, we investigated the antimicrobial activity of the ethyl acetate fraction (EAF) obtained from the leaf hydroalcoholic extract of A. glabra. EAF was bactericidal against different strains of P. aeruginosa. EAF also presented with a time- and concentration-dependent effect on P. aeruginosa viability. Testing of different EAF sub-fractions showed that the sub-fraction 32-33 (SF32-33) was the most effective against P. aeruginosa. Analysis of the chemical constituents of SF32-33 demonstrated a high content of flavonoids. Incubation of this active sub-fraction with P. aeruginosa ATCC 27983 triggered an endothermic reaction, which was accompanied by an increased electric charge, suggesting a high binding of SF32-33 compounds to bacterial cell walls. Collectively, our results suggest that A. glabra-derived compounds, especially flavonoids, may be useful for treating infections caused by P. aeruginosa.

show abstract

“…A docking study was performed for the tested compounds 2a, 2b, 2d, and 2e in order to scrutinize their possible interactions with gyrase B (GyrB43) from E. coli (PDB code: 4PRV; resolution 2.00 Å) by employing the docking module that was implemented in the MOE software. The bacterial DNA gyrase has been reported as a good target for antibacterial agents and the assessment of potential antibacterial activity of new compounds [18]. Figure 9 presents the best docking poses for the novel flavanone bearing chromene moiety inside the GyrB binding pocket.…”

Section: Docking Studiesmentioning

confidence: 99%

“…The overexpression of the cyclin-dependent kinase-2 (CDK2) has been documented in various categories of human tumors [12][13][14][15][16][17]. Molecular docking evaluations have been executed to acquire an additional comprehension of the binding behavior of the generated molecules with CDK2 (Protein Data Bank (PDB) ID: 1FVV) as well as gyrase B (GyrB43) from Escherichia coli (PDB code: 4PRV), which has been reported to be a target for analyzing antibacterial activities [18].…”

Section: Introductionmentioning

confidence: 99%

“…The antibacterial activities of flavonoids have been reported to be correlated with their chemical structures [29][30][31][32]. However, the quantitative structure-activity relationship (QSAR) for flavonoids as antibacterial agents has been capturing interest through the quantitative construction of associations between the molecular structures or properties with a variation in biological activities [18,33]. It is significant that anticancer activity, which is comprised of the most interesting pharmacological properties of flavonoids [34], proceeds via a unique mechanism, and aids in the prevention of cancer growth through the flavonoids' ability to function as anti-oxidants [35][36][37], enzyme inhibitors [38], and growth regulators [39].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties

et al. 2020

View full text Add to dashboard Cite

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

show abstract

3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

Cited by 75 publications

References 46 publications

Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

Annona glabra Flavonoids Act As Antimicrobials by Binding to Pseudomonas aeruginosa Cell Walls

Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties

Contact Info

Product

Resources

About