scholarly journals Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3353
Author(s):  
Nor Atiqah Jusril ◽  
Ain Nur Najihah Muhamad Juhari ◽  
Syahrul Imran Abu Bakar ◽  
Wan Mazlina Md Saad ◽  
Mohd Ilham Adenan
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Active Sites ◽  
In Vitro Study ◽  
Centella Asiatica ◽  
Ache Inhibitor ◽  
Asiatic Acid ◽  
In Silico Docking ◽  
Ache Inhibitory Activity

Alzheimer’s disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman’s spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.

scholarly journals Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 416
Author(s):  
Sami I. Alzarea ◽  
Abeer H. Elmaidomy ◽  
Hani Saber ◽  
Arafa Musa ◽  
Mohammad M. Al-Sanea ◽  
...  
Keyword(s):  
Red Sea ◽  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
Brown Algae ◽  
In Silico ◽  
Active Sites ◽  
In Vitro Study ◽  
Lipoxygenase Inhibitors ◽  
Phytochemical Investigation

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum “Sargassaceae” dereplicated eleven compounds 1–11. Further phytochemical investigation afforded two new aryl cresol 12–13, along with eight known compounds 14–21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes’ active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.

scholarly journals ANTICHOLINESTERASE ACTIVITY OF OCTA PEPTIDES RELATED TO HUMAN HISTATIN 8: IN-SILICO DRUG DESIGN AND IN-VITRO

2017 ◽  
Vol 10 (6) ◽  
pp. 115 ◽  
Author(s):  
Pandurangan Perumal ◽  
Mani Vasudevan ◽  
Sridevi Chigurupati ◽  
Manikandan Selvaraj
Keyword(s):  
In Silico ◽  
Potent Inhibitor ◽  
Docking Study ◽  
Ache Inhibitor ◽  
In Silico Docking ◽  
In Silico Drug Design ◽  
Ic50 Value ◽  
Ache Inhibitory Activity ◽  
Histatin 8

Objective: To evaluate the octapeptides related to human histatin 8 by in-silico and in-vitro studies.Method: Schrodinger, LLC and Ellman’s method.Results: The compound HH1 and HH2 was found to be potent docking score of −9.494 and −7.401 against acetylcholinesterase (AChE) enzyme. The IC50 value of HH1 and HH2 was found to be 0.39±0.28 and 0.78±0.15 μg/mL. However, these compounds are shown to be highly effective as compared with the control AChE inhibitor donepezil (0.065±0.0050 μg/mL).Conclusion: In-silico docking study was conducted for the designed octapeptides related to human histatin 8 against AChE enzyme shows significance binding affinity toward HH1 and HH2 peptides and the AChE inhibitory activity of octapeptides shown to be a highly potent inhibitor as compared with control donepezil.

scholarly journals In silico docking studies and in vitro xanthine oxidase inhibitory activity of commercially available terpenoids

2012 ◽  
Vol 2 (5) ◽  
Author(s):  
MUTHUSWAMY UMAMAHESWARI ◽  
Preetha Prabhu ◽  
KUPPUSAMY ASOKKUMAR ◽  
THIRUMALAISAMY SIVASHANMUGAM ◽  
Varadharajan Subhadradevi ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Docking Studies ◽  
In Silico Docking

scholarly journals Dual BACE1 and Cholinesterase Inhibitory Effects of Phlorotannins from Ecklonia cava—An In Vitro and in Silico Study

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 91 ◽  
Author(s):  
Jinhyuk Lee ◽  
Mira Jun
Keyword(s):  
In Silico ◽  
In Vitro Study ◽  
Kinetic Studies ◽  
Binding Energies ◽  
Ecklonia Cava ◽  
Hydroxyl Groups ◽  
Inhibitory Effects ◽  
In Silico Docking ◽  
Ache Inhibitors

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases with a multifactorial nature. β-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic β-amyloid (Aβ) and the promotion of Aβ fibril formation, respectively, are considered as prime therapeutic targets for AD. In our efforts towards the development of potent multi-target, directed agents for AD treatment, major phlorotannins such as eckol, dieckol, and 8,8′-bieckol from Ecklonia cava (E. cava) were evaluated. Based on the in vitro study, all tested compounds showed potent inhibitory effects on BACE1 and AChE. In particular, 8,8′-bieckol demonstrated the best inhibitory effect against BACE1 and AChE, with IC50 values of 1.62 ± 0.14 and 4.59 ± 0.32 µM, respectively. Overall, kinetic studies demonstrated that all the tested compounds acted as dual BACE1 and AChE inhibitors in a non-competitive or competitive fashion, respectively. In silico docking analysis exhibited that the lowest binding energies of all compounds were negative, and specifically different residues of each target enzyme interacted with hydroxyl groups of phlorotannins. The present study suggested that major phlorotannins derived from E. cava possess significant potential as drug candidates for therapeutic agents against AD.

In vitro and in vivo activities of imipenem combined with BLI-489 against class D β-lactamase-producing Acinetobacter baumannii

2020 ◽  
Author(s):  
Yung-Chih Wang ◽  
Shu-Wei Huang ◽  
Ming-Hsien Chiang ◽  
I-Ming Lee ◽  
Shu-Chen Kuo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Active Sites ◽  
Synergistic Effects ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Class D ◽  
Time Kill

Abstract Background According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like β-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). Objectives In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D β-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. Methods A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time–kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. Results Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time–kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. Conclusions Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids

Planta Medica ◽  
2017 ◽  
Vol 83 (11) ◽  
pp. 901-911 ◽  
Author(s):  
Lucia Crascì ◽  
Livia Basile ◽  
Annamaria Panico ◽  
Carmelo Puglia ◽  
Francesco Bonina ◽  
...  
Keyword(s):  
Active Site ◽  
Inhibitory Activity ◽  
In Silico ◽  
In Silico Docking ◽  
Lead Compounds ◽  
Good Ability ◽  
Metalloprotease Inhibitors ◽  
Ic50 Values ◽  
Further Development

AbstractMetalloproteases are a family of zinc-containing endopeptidases involved in a variety of pathological disorders. The use of flavonoid derivatives as potential metalloprotease inhibitors has recently increased.Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin, apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside, and 7-O-glucuronide).The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized correlating in vitro target-oriented screening and in silico docking.The flavones apigenin, luteolin, and their respective glucosides have good ability to interact with metalloproteases and can also be lead compounds for further development. Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1, MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50 values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring to the active site of MMP-1, -3, -8, -9, and -13. Overall, the in silico data are substantially in agreement with the in vitro ones (fluorimetric assay).

scholarly journals ANTICANCER ACTIVITY OF Β-SITOSTEROL FROM PLECTRANTHUS AMBOINICUS (LOUR. SPRENG.) LEAVES: IN VITRO AND IN SILICO STUDIES

2017 ◽  
Vol 10 (5) ◽  
pp. 306
Author(s):  
Denny Satria ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Panal Sitorus
Keyword(s):  
In Silico ◽  
Estrogen Receptor Alpha ◽  
In Vitro Study ◽  
Three Dimensions ◽  
Three Dimension ◽  
Docking Score ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Her 2

Objective: β-sitosterol is the steroid compound which is an important nutrient in the diet meal, hydrophobic and soluble in organic solvents and considered as a good biomarker due to its biological activity.Methods: In vitro study was using 2,5-diphenyl tetrazolium bromide method towards T47D, MCF-7, HeLa, and WiDr cell lines. In silico docking using PLANTS program and visualized by Yasara program. The model of three dimension enzyme structures used in this research were epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K), estrogen receptor-alpha (ER-α), ER-beta (ER-β), and human EGFR 2 (HER-2). Two and three dimensions of β-sitosetrol, ZSTK474, and tamoxifen as the standard were generated using Marvin Sketch program.Results: β-sitosterol was found to have inhibitory concentration 50% of 0.55; 0.87; 0.76, and 0.99 mM. β-sitosterol and ZSTK474 were inhibited EGFR and PI3K with docking score −92.8195; −91.7920 and −91.7470; −94.7491 β-sitosterol and tamoxifen were inhibited ER-α, ER-β and HER-2 with docking score −78.5570; −89.535, −68.7717; −52.008 and −90.4908; −50.5576, respectively.Conclusion: Based on the results above that shows β-sitosterol provide effective as anticancer.Keywords: β-sitosterol, Inhibitor, Anticancer, In vitro, In silico.

scholarly journals New 5-LOX and 15-LOX Inhibitors Isolated from Red Sea Derived Brown Alga Sarragassum Cinnerum: An In Silico-Supported Study

2021 ◽  
Author(s):  
Sami I. Alzarea ◽  
Abeer H. Elmaidomy ◽  
Hani Saber ◽  
Arafa Musa ◽  
Mohammad M. Al-Sanea ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
In Silico ◽  
Active Sites ◽  
Tropical Region ◽  
Phytochemical Investigation ◽  
Development Processes ◽  
Algal Genus ◽  
Lox Inhibitors

Abstract Sargassum is a brown algal genus inhabiting tropical region. Metabolomic profiling of Sarragassum cinnerum “Sargassaceae”, dereplicated eleven compounds 1-11, further phytochemical investigation afforded two new aryl cresol 12-13, along with eight known compounds 14-21. Both new metabolites along with 19 showed moderate in vitro antiproliferative activity against HEPG2, MCF7, and CACO2. Molecular targets of the bioactive compounds using a pharmacophore-based virtual screening, predicts 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The validation step revealed 12 and 13 inhibited 5-LOX more prudentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico analysis revealed the molecular interactions inside both enzymes active sites and explained the varying inhibitory activity for 12, and 13 toward 5-LOX and 15-LOX. Taken together, unique metabolites in S. cinnerum had potential anticancer activity supported with in-silico investigations to facility drug discovery and development processes.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

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