Aurones and furoaurones: Biological activities and synthesis

Hassan, Ghada S.; Georgey, Hanan H.; George, Riham F.; Mohamed, Eman

doi:10.1016/j.bfopcu.2018.06.002

Cited by 27 publications

(17 citation statements)

References 37 publications

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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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Section: Introductionmentioning

confidence: 99%

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

Hadni

Elhallaoui

2020

Heliyon

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“…They are also considered phytoalexins produced by plants in response to pathogen attack [ 33 ]. Aurone derivatives have been reported to possess different bio-activities [ 34 ], such as anti-inflammatory [ 35 ], antibacterial [ 36 ], anti-malarial [ 37 , 38 ], anti-hepatitis [ 39 , 40 ], antioxidant [ 41 , 42 , 43 , 44 ], anticancer [ 45 , 46 , 47 , 48 , 49 ], and others. However, their ability to inhibit HPL has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations

et al. 2020

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Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of −10.6 kcal⋅mol−1, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

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“…The test compounds consisted of 82 aurone derivatives (symbols A1 to A82) collected from scientific papers investigating the biological effects of aurone derivatives [10,[15][16][17][18][19][20]. The 2D structures of these compounds were drawn by ISIS Draw 2.5 program and formatted in the MOL file.…”

Section: Ligandmentioning

confidence: 99%

“…Aurone is often found in some species of the Scrophulariaceae and Compositae families [8,9]. Many of the biological effects of aurone derivatives have been studied and published as anticancer, anti-inflammatory, antifungal, antibacterial, anti-malarial, anti-hepatitis B, anti-oxidant, etc [10].…”

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confidence: 99%

AURONE AS PROMISING HUMAN PANCREATIC LIPASE INHIBITORS THROUGH <em>IN SILICO</em> STUDY

Nguyen

Huynh

Tran

2019

Proceedings of the 23rd International Electronic Conference on Synthetic Organic Chemistry

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In this study, 82 aurone compounds, a subclass of flavonoids were investigated towards to human pancreatic lipase inhibitory activity. Molecular docking of the aurones was done successfully into the catalytic position of lipase (Pdb: 1LPB) using AutoDock Vina software 1.5.7.rc1. The results showed that 62 compounds interacted well with residues in the catalytic trial Ser152-Asp176-His263 and Phe77 of protein 1LPB. In particular, A32 was selected as the best binding compound (docking score: -10.6 kcal.mol -1 ) and suitable for oral drug following the 5-Lipinski rule. Combining the results of docking and molecular dynamics simulation of A32-protein complex during 10 ns, this study performed that the A32 compound bound well and formed a stable complex with 1LPB protein. Therefore, the A32 compound was considered as the lead compound which could be synthesized and tested for pancreatic lipase inhibitor.Obesity is considered as a complex disease, with a variety of factors and causes, in which the most commonly is an unreasonable diet and unhealthy lifestyle leading to an imbalance between energy supplement and energy consumption in the body [1]. It opens up the way for for the obesity drug research, which is the inhibition of fat hydrolysis of human pancreatic lipase (HPL). Cause, HPL along with co-factors Colipase and Ca2+, play a main role in the process digestion and absorption of fat. HPL hydrolyzes 50 -70% of the total fat from the food, so inhibiting HPL will significantly reduce the amount of absorbed fat [2,3].Nowadays, many in silico models are being applied to finding potential bioactive compounds for the treatment of obesity [2,4,[5][6][7]. These models made the new drug research more clearly oriented and helped to save both cost and time. Besides that, there is a need to develop new drugs having fewer side effects and more safety, specifically taking from natural compounds for HPL inhibitory activities. The results have discovered natural compounds belonging to many different groups of structures such as saponins, alkaloids, carotenoids, flavonoids that inhibited HPL enzyme [2,4]. In particular, flavonoids with subclasses such as flavone, flavonole, chalcone have been extensively studied and the researches obtained many good HPL inhibition results with the IC50 values determined as Licochalcone A (IC50 35 µg/ml) [5], Galangin (IC50 48.20 mg/ml) [6], Hesperidin (IC50

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Aurones and furoaurones: Biological activities and synthesis

Cited by 27 publications

References 37 publications

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

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

Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations

AURONE AS PROMISING HUMAN PANCREATIC LIPASE INHIBITORS THROUGH <em>IN SILICO</em> STUDY

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