Aurone
215727068
An Aurone Derivative Revealing the Metabolism of Lipid Droplets and Monitoring Oxidative Stress in Living Cells.
Lipid droplets (LDs) are closely connected with many physiological processes and abnormal LDs are related to many diseases. Herein, a family of two photon fluorescence compounds based on the aurone skeleton were developed as efficient LDs imaging probes. They exhibit the obvious solvatochromism effect from blue to orange emission ~140 nm shift) in various solvents. The robust probes possess low toxicity to living cells, high photobleaching resistance and superior photostability and can light up LDs with high specificity. Furthermore, the probe DMMB was carefully applied in real time monitoring the morphological changes of LDs and the interactions between LDs and mitochondria under specific physiological conditions (e.g. starvation) We have observed for the first time the dynamic change between mitochondria and LDs when mitochondrial damage is caused by a large excess of H2O2 in a short time.
Analytical chemistry
Kang-Nan Wang Shuyue Ma Yanyan Ma Yuping Zhao Miaomiao Xing Liyu Zhou Duxia Cao Weiying Lin
216061332
3D QSAR, docking and ADMET properties of aurone analogues as antimalarial agents
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 (Q2 0.5; R2 0.97; Rpred2 0.72) and the best CoMSIA model (Q2 0.526; R2 0.915; Rpred2= 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 bL, 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.
Heliyon
Hanine Hadni Menana Elhallaoui
225251153
Synthesis of 1,2,3,4 Tetrahydrobenzofuro[3,2 d ]pyrimidines via [4+2] Annulation Reaction of 1,3,5 Triazinanes and Aurone Derived a,b Unsaturated Imines
Bin Cheng Xinping Zhang Shengxian Zhai Yixuan He Qingqing Tao Hui Li Jianpeng Wei Haiyan Sun Taimin Wang Hongbin Zhai
223555996
Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations
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 kcalmol 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.
Molecules
Phuong Thuy Viet Nguyen Han Ai Huynh Dat Van Truong Thanh-Dao Tran Cam-Van Thi Vo
218686085
Identification of Anti tuberculosis Compounds From Aurone Analogs
The emergence of multidrug resistant Mycobacterium tuberculosis (Mtb) strains has made tuberculosis (TB) control more difficult. Aurone derivatives have demonstrated promising anti bacterial activities, but their effects against Mtb have not been thoroughly determined. In this study, we aimed to develop anti TB compounds from aurone analogs. We used a fluorescent protein tdTomato labeled Mtb CDC1551 strain to screen 146 synthesized aurone derivatives for effective anti TB compounds. The 9504, 9505, 9501, 9510, AA2A, and AA8 aurones inhibited the growth of Mtb with minimal inhibitory concentrations of 6.25, 12.5, 25, 25, 25, and 50 mM, respectively. We also examined cytotoxicities of the six leads against the human liver cell line HepG2, the primate kidney cell line Vero and human monocyte THP 1 derived macrophages. Three of the aurone leads (9504, 9501, and 9510) showed low cytotoxic effects on all three cell lines and high Mtb inhibitory efficacy (selectivity index 10) Aurone 9504, 9501, AA2A, or AA8 significantly reduced the Mtb load in the lungs of infected mice after a 12 days treatment. We determined that the aurone leads inhibit Mtb chorismate synthase, an essential enzyme for aromatic acid synthesis. Our studies demonstrate the promise of synthetic aurones as novel anti TB therapeutics.
Frontiers in Microbiology
Dong Yang Zachary E Taylor Scott T Handy Shaoji Li Jiawang Liu Jennifer M Stabenow Lillian Zalduondo Colleen B Jonsson Elliot Altman Ying Kong
219983768
Bioactivity guided isolation of aurone derivatives with hepatoprotective activities from the fruits of Cucumis bisexualis
Abstract Bioactivity guided phytochemical investigation of Cucumis bisexualis has led to the isolation of three new coumarin aurone heterodimers (1 3) along with six aurone derivatives (4 9) were isolated from C. bisexualis for the first time. Their structures were determined by their extensive spectroscopic data and comparison with the values reported in the references. All isolated compounds (1 9) were evaluated for their hepatoprotective activities on human L O2 cells, which compared with positive control of Bifendatatum. Among them, compounds 1, 2, and 7 exhibited moderate hepatoprotective activities to promote effects on the proliferation of L O2 cells.
Zeitschrift fur Naturforschung. C, Journal of biosciences
Qinge Ma Rongrui Wei Zhipei Sang
226279970
Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni.
Schistosomiasis is a neglected disease caused by helminth flatworms of the genus Schistosoma, affecting over 240 million people in more than 70 countries. The treatment relies on a single drug, praziquantel, making urgent the discovery of new compounds. Aurones are a natural type of flavonoids that display interesting pharmacological activities, particularly as chemotherapeutic agents against parasites. In pursuit of treatment alternatives, the present work conducted an in vitro and in vivo antischistosomal investigation with aurone derivatives against Schistosoma mansoni. After preparation of aurone derivatives and their in vitro evaluation on adult schistosomes, the three most active aurones were evaluated in cytotoxicity and haemolytic assays, as well as in confocal laser scanning microscope studies, showing tegumental damage in parasites in a concentration dependent manner with no haemolytic or cytotoxic potential toward mammalian cells. In a mouse model of schistosomiasis, at a single oral dose of 400 mg/kg, the selected aurones showed worm burden reductions of 35% to 65.0% and egg reductions of 25% to 70.0% The most active thiophenyl aurone derivative 18, unlike PZQ, had efficacy in mice harboring juvenile S. mansoni, also showing significant inhibition of oviposition by parasites, giving support for the antiparasitic potential of aurones as lead compounds for novel antischistosomal drugs.
Acta tropica
Vinicius R D Pereira Ligia Souza da Silveira Ana C Mengarda Ismael Jose Alves Junior Ohana Oliveira Zuza da Silva Fabio Balbino Miguel Marcos P N Silva Ayla das Chagas Almeida Daniel da Silva Torres Priscila de Faria Pinto Elaine Soares Coimbra Josue de Moraes Mara Rubia Costa Couri Ademar Alves Da Silva Filho
225268887
The first synthesis of peracetyl glycosyl aurone derivatives and aurone glucosides
Abstract Aurones, a sub class of the flavonoids with proven therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O glycosylation was achieved by reacting 6 hydroxy aurones with 2, 3, 4, 6 tetra O acetyl a D glucopyranosyl bromide in the presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB) The successful synthesis of aurone glycosides (33 examples) in 60 92% yield will benefit the synthesis of combinatorial libraries of glycosylated aurones for their biological study and comparison with non glycosylated aurones.
Arjun Kafle Shrijana Bhattarai Scott T Handy
219561624
Copper(i) catalyzed synthesis of selanyl methylene 4 chromanol and aurone derivatives.
An efficient copper catalyzed cyclization cascade approach towards highly functionalized methylene 4 chromanol and aurone derivatives has been developed from reactions of ynols via 6 exo dig and 5 exo dig cyclization respectively. The catalysis involves alkyne activation via diorgano diselenides and also their regioselective incorporation into the methylene 4 chromanol and aurone derivative core and is an open air transformation.
Organic biomolecular chemistry
Sushree Ranjan Sahoo Debayan Sarkar Felix Henkel Hans Reuter
210996656
Anticolon Cancer Potential of (2Z) 2 (4' Hydroxyphenyl) Methylene] 6 Methoxy 7 Prenyl 3(2H) Benzofurane, a New Aurone From Psoralea corylifolia
A new aurone, (2Z) 2 (4' hydroxyphenyl) methylene] 6 methoxy 7 prenyl 3(2H) benzofurane (1) together with 6 known compounds (2 7) was isolated from the EtOAc soluble extract of the seeds of Psoralea corylifolia. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for in vitro inhibitory activity against a human colon cancer cell line (SW620) Compounds 1 to 3 showed moderate cytotoxicity against the SW620 cells with IC50 values ranging from 24.31 to 28.72 mM. Among these compounds, 1 showed higher cytotoxicity against SW620 cells with an IC50 value of 24.31 mM.
A H Liu Li-hua Liu Chun-Ying Liu