Aurone: A biologically attractive scaffold as anticancer agent

Alsayari, Abdulrahman; Muhsinah, Abdullatif Bin; Hassan, Mohd. Zaheen; Ahsan, Mohamed Jawed; Alshehri, Jaber Abdullah; Begum, Naseem

doi:10.1016/j.ejmech.2019.01.078

Cited by 79 publications

(45 citation statements)

References 81 publications

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“…Our results are also in agreement with a prior study reporting that aurones arrest the cell cycle via targeting (CDK) protein Cdc28, making aurones a promising candidate for cancer therapy [12]. Among different aurone derivatives synthesized as potential anticancer agents, aurone compounds that possess a methoxy group at position 4 on ring B, like aurone SH1009, were found to produce an enhanced antiproliferative activity by significantly arresting the cell cycle at G2/M phase [83]. In our study, fluorescent imaging was performed to detect actin cytoskeleton depolarization as a consequence of aurone SH1009 perturbation of rearrangement of actin patches in the bud site at the end of G1 phase, leading to cell cycle arrest at G1 phase.…”

Section: Discussionsupporting

confidence: 91%

“…However, since the first yeast deletion collection was created in 2002 [79], chemogenomic profiling has been proven as a powerful system for characterizing the mode of action and molecular targets of several drugs [80], as well as thousands of additional bioactive molecules [81, 82]. A considerable number of studies have been recently reviewed the broad spectrum of biological activities of aurone compounds as anticancer agents identified using phenotype-based approaches, exploiting the existing knowledge of a given cellular process inhibited by aurones, including inhibition of CDKs, DNA scissoring, histone deacetylase, topoisomerase, ATP-binding cassette transporter, and tubulin polymerization [83]. In contrast, here, a genetic-based approach was applied to comprehensively reveal all the biological effects of aurone treatment as a potential antimicrobial.…”

Section: Discussionmentioning

confidence: 99%

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Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound

et al. 2019

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Every year, more than 250,000 invasive candidiasis infections are reported with 50,000 deaths worldwide. The limited number of antifungal agents necessitates the need for alternative antifungals with potential novel targets. The 2-benzylidenebenzofuran-3-(2H)-ones have become an attractive scaffold for antifungal drug design. This study aimed to determine the antifungal activity of a synthetic aurone compound and characterize its mode of action. Using the broth microdilution method, aurone SH1009 exhibited inhibition against C. albicans, including resistant isolates, as well as C. glabrata, and C. tropicalis with IC50 values of 4–29 μM. Cytotoxicity assays using human THP-1, HepG2, and A549 human cell lines showed selective toxicity toward fungal cells. The mode of action for SH1009 was characterized using chemical-genetic interaction via haploinsufficiency (HIP) and homozygous (HOP) profiling of a uniquely barcoded Saccharomyces cerevisiae mutant collection. Approximately 5300 mutants were competitively treated with SH1009 followed by DNA extraction, amplification of unique barcodes, and quantification of each mutant using multiplexed next-generation sequencing. Barcode post-sequencing analysis revealed 238 sensitive and resistant mutants that significantly (FDR P values ≤ 0.05) responded to aurone SH1009. The enrichment analysis of KEGG pathways and gene ontology demonstrated the cell cycle pathway as the most significantly enriched pathway along with DNA replication, cell division, actin cytoskeleton organization, and endocytosis. Phenotypic studies of these significantly enriched responses were validated in C. albicans. Flow cytometric analysis of SH1009-treated C. albicans revealed a significant accumulation of cells in G1 phase, indicating cell cycle arrest. Fluorescence microscopy detected abnormally interrupted actin dynamics, resulting in enlarged, unbudded cells. RT-qPCR confirmed the effects of SH1009 in differentially expressed cell cycle, actin polymerization, and signal transduction genes. These findings indicate the target of SH1009 as a cell cycle-dependent organization of the actin cytoskeleton, suggesting a novel mode of action of the aurone compound as an antifungal inhibitor.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound

et al. 2019

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“…Aurones (2-arylidenebenzofuran-3(2H)-ones) ( Figure 1), and azaaurones (2-araylideneindol-3(2H)ones) ( Figure 2), belong to the flavonoid family containing an exocyclic double bond. Aurones have been reported to have important biological activities [8,9], including anticancer [10,11], antimicrobial [12], antileishmanial [13], anti-alzheimer [14] antiparasitic [15], antifungal [16] and anti-inflammatory [17] activity. In a particular way, aurones and azaaurones have shown a high antimalarial activity because they act as dual-stage antimalarial agent, i.e.…”

Section: Introductionmentioning

confidence: 99%

3D-QSAR, docking and ADMET properties of aurone analogues as antimalarial agents

Hadni

Elhallaoui

2020

Heliyon

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The development of multi-resistant strains of plasmodium parasite has become a global problem, therefore, the discovery of new antimalarial agents is the only available solution. In order to improve and propose new compounds with antimalarial activity, the three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking studies were carried on aurone analogues acting as Qo site inhibitors in cytochrome b. The 3D-QSAR model was established in this study based on the Comparative Molecular Field Analysis (CoMFA) and the Comparative Molecular Similarity Indices Analysis (CoMSIA). The good predictability was obtained using the CoMFA model (Q 2 ¼ 0.5; R 2 ¼ 0.97; R 2 pred ¼ 0.72) and the best CoMSIA model (Q 2 ¼ 0.526; R 2 ¼ 0.915; R 2 pred ¼ 0.765). The predictive capacity of the developed model was evaluated through external validation using a test set compound and an applicability domain technique. In this study, the Steric, electrostatic and hydrogen bond acceptor fields played a key role in antimalarial activity. The results of the molecular docking revealed theoretically the importance of the residues his183 and his82 in the active site of the heme b L , this result was validated by a new assessment method. Based on the previous results, we designed several new potent Cytochrome b inhibitors and their inhibitory activities were predicted by the best model. Furthermore, these new inhibitors were analyzed for their ADMET properties and drug likeness. These results would be of great help in leading optimization for new drug discovery that can solve the problem of multiple drug resistance.

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“…The anthochlor pigment aurone was first isolated by Geissman and Heaton from the flowers of Coreopsis grandiflora in 1943 and was the first representative structure isolated from a natural source. Besides flowering plants, the other major sources of aurones are bryophytes, gymnosperms and brown algae . Plant uses aurones as phytoalexin, which acts as defendant counter to numerous infections .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Quinoline‐Based Novel Aurones

et al. 2020

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A new series of quinoline based aurones 7(a–n) has been synthesized and evaluated for their antibacterial, antifungal and antiquorum sensing activities. These novel aurones have been prepared directly from 2‐chloro‐1‐(2,4‐dihydroxyphenyl)ethan‐1‐one in one pot, by reacting it with differently substituted 2‐chloroquinoline‐3‐carbaldehydes using activated barium hydroxide under solvent free grinding conditions. Structures of these novel aurones are in agreement with their IR, 1H‐NMR, 13C‐NMR and HRMS data. Some of these compounds have attributed a significant antiquorum sensing activity.

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Aurone: A biologically attractive scaffold as anticancer agent

Cited by 79 publications

References 81 publications

Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound

Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound

3D-QSAR, docking and ADMET properties of aurone analogues as antimalarial agents

Synthesis and Biological Evaluation of Quinoline‐Based Novel Aurones

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