Evaluation of the Antioxidant, Antidiabetic, and Antiplasmodial Activities of Xanthones Isolated from Garcinia forbesii and Their In Silico Studies

This study aimed to isolate xanthones from Garcinia forbesii and evaluated their activity in vitro and in silico. The isolated compounds were evaluated for their antioxidant activity by DPPH, ABTS and FRAP methods. The antidiabetic activity was performed against α-glucosidase and α-amylase enzymes. The antiplasmodial activity was evaluated using Plasmodium falciparum strain 3D7 sensitive to chloroquine. Molecular docking analysis on the human lysosomal acid-alpha-glucosidase enzyme (5NN8) and P. falciparum lactate dehydrogenase enzyme (1CET) and prediction of ADMET for the active compound, were also studied. For the first time, lichexanthone (1), subelliptenone H (2), 12b-hydroxy-des-D-garcigerrin A (3), garciniaxanthone B (4) and garcigerin A (5) were isolated from the CH2Cl2 extract of the stem bark of G. forbesii. Four xanthones (Compounds 2–5) showed strong antioxidant activity. In vitro α-glucosidase test showed that Compounds 2 and 5 were more active than the others, while Compound 4 was the strongest against α-amylase enzymes. In vitro antiplasmodial evaluation revealed that Compounds 2 and 3 showed inhibitory activity on P. falciparum. Molecular docking studies confirmed in vitro activity. ADMET predictions suggested that Compounds 1–5 were potential candidates for oral drugs. The isolated 2–5 can be used as promising phytotherapy in antidiabetic and antiplasmodial treatment.

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IN SILICO STUDIES ON FUNCTIONALIZED AZAGLYCINE DERIVATIVES CONTAINING 2, 4-THIAZOLIDINEDIONE SCAFFOLD ON MULTIPLE TARGETS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i8.19835 ◽

2017 ◽

Vol 9 (8) ◽

pp. 209 ◽

Cited By ~ 4

Author(s):

Arifa Begum ◽

Shaheen Begum ◽

Prasad Kvsrg ◽

Bharathi K.

Keyword(s):

Molecular Docking ◽

Oral Bioavailability ◽

In Silico ◽

Viral Infections ◽

Target Prediction ◽

Docking Studies ◽

Antidiabetic Activity ◽

Molecular Docking Studies ◽

In Silico Studies ◽

Glycine Derivative

Objective: The 2, 4-thiazolidinedione containing compounds could lead to most promising scaffolds with higher efficiency toward the targets recognized for its antidiabetic activity when combined with azaglycine moiety. The objective of the present work was to merge functionalized aza glycines with 2, 4-thiazolidinediones, perform in silico evaluation by molecular properties prediction and undertake the molecular docking studies with targets relevant to diabetes, bacterial and viral infections using Swiss Dock programme for unraveling the target identification which can be used for further designing.Methods: (i) In silico studies were performed using Molinspiration online tool, Swiss ADME website and Swiss Target Prediction websites to compute the physicochemical descriptors, oral bioavailability and brain penetration. (ii) Molecular docking studies were performed using Swiss Dock web service for enumeration of binding affinities and assess their biological potentiality.Results: The results predicted good drug likeness, solubility, permeability and oral bioavailability for the compounds. All the compounds showed good docking scores as compared to the reference drugs. The N-oleoyl functionalized aza glycine derivative demonstrated superior binding properties towards all the studied target reference proteins, suggesting its significance in pharmacological actions.Conclusion: The binding interactions observed in the molecular docking studies suggest good binding affinity of the oleoyl functionalized aza glycine derivative, indicating that this derivative would be a promising lead for further investigations of anti-viral, anti-inflammatory and anti-diabetic activities.

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In vitro and in silico studies on AChE inhibitory effects of a series of donepezil-like arylidene indanones

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0356 ◽

2020 ◽

Vol 45 (4) ◽

pp. 359-363

Author(s):

Belgin Sever ◽

Mehlika Dilek Altıntop ◽

Halide Edip Temel

Keyword(s):

Molecular Docking ◽

In Silico ◽

Binding Mode ◽

Docking Studies ◽

Ache Inhibitor ◽

Ache Inhibition ◽

Lipinski’S Rule ◽

In Silico Studies ◽

Orally Bioavailable

AbstractObjectiveDonepezil is the most potent acetylcholinesterase (AChE) inhibitor currently available on the market for the management of Alzheimer’s disease. In this study, it was aimed to identify potent donepezil analogues.Materials and methodsThe effects of arylidene indanones (1–10) on AChE inhibition were examined using modified Ellman’s assay. Compound 4, the most potent arylidene indanone in this series, was subjected to molecular docking to anticipate its binding mode in the AChE site (PDB code: 4EY7). The pharmacokinetic profiles of all derivatives were also predicted.ResultsCompound 4 was found as the most potent AChE inhibitor with an IC50 value of 5.93 ± 0.29 μg/mL. According to molecular docking studies, compound 4 presented favorable interactions such as π–π interactions with Trp286 and Tyr337. In silico studies revealed that the compound did not violate Lipinski’s rule of five and Jorgensen’s rule of three, making it a potential orally bioavailable agent.ConclusionCompound 4 is a feasible candidate for further experiments related to AChE inhibition.

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Biological Activity Evaluation and In Silico Studies of Polyprenylated Benzophenones from Garcinia celebica

Biomedicines ◽

10.3390/biomedicines9111654 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1654

Author(s):

Yenni Pintauli Pasaribu ◽

Arif Fadlan ◽

Sri Fatmawati ◽

Taslim Ersam

Keyword(s):

Antioxidant Activity ◽

Molecular Docking ◽

Cell Lines ◽

In Silico ◽

Oral Drug ◽

Root Bark ◽

Falciparum Strain ◽

In Silico Studies ◽

Mcf 7

This study aimed to isolate polyprenylated benzophenones from the rootbark of Garcinia celebica and assess their activities in vitro and in silico. The antioxidant activity was evaluated by the DPPH, ABTS, and FRAP methods. The cytotoxicity was evaluated against HeLa, MCF-7, A549, and B16 cancer cell lines. The antiplasmodial activity was performed against the chloroquine-sensitive Plasmodium falciparum strain 3D7. Molecular docking was analyzed on alpha-estrogen receptor (3ERT) and P. falciparum lactate dehydrogenase enzyme (1CET). The prediction of ADMET for the compounds was also studied. For the first time, (-)-cycloxanthochymol, isoxanthochymol, and xanthochymol were isolated from the root bark of Garcinia celebica. The antioxidant and cytotoxicity evaluation showed that all benzophenones exhibited antioxidant activity compared to gallic acid and quercetin as positive controls and also exhibited strong activity against HeLa, MCF-7, A549, and B16 cell lines compared to cisplatin as the positive control. The antiplasmodial evaluation showed that isoxanthochymol exhibited activity against the chloroquine-sensitive P. falciparum strain 3D7. In addition, the in silico molecular docking study supported in vitro activities. The ADMET analysis also indicated the isolated benzophenones are potential oral drug candidates.

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EVALUATION OF ANTI-DIABETIC ACTIVTY OF DIFFERENT EXTRACTS OF MYRISTICA FRAGRANS HOUTT: IN VITRO AND IN SILICO STUDIES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i4.16720 ◽

2017 ◽

Vol 10 (4) ◽

pp. 275

Author(s):

Saranya Sivaraj ◽

Gomathi Kannayiram ◽

Gayathri Dasararaju

Keyword(s):

Molecular Docking ◽

In Silico ◽

Inhibitory Effect ◽

Docking Studies ◽

Alpha Amylase ◽

Myristica Fragrans ◽

In Silico Studies ◽

Myristica Fragrans Houtt ◽

In Silico Molecular Docking

Objective: This study is aimed to evaluate the anti-diabetic effect of sequentially extracted (hexane, dichloromethane, ethyl acetate, and ethanol) Myristica fragrans houtt (mace) through in vitro and in silico studies. Methods: The in vitro anti-diabetic effect of the sequentially extracted plant were evaluated for its alpha-amylase inhibitory activity and the potential binding was studied by in silico studies using Schrödinger Maestro.Results: All extracts showed dose dependent alpha-amylase inhibitory effect. At concentration 500 µg/ml, all the extracts showed more than 60% inhibition of the alpha-amylase enzyme and the highest inhibition (81.30%) at 500 µg/ml was observed in DCM extract of mace. Potential compounds were identified by in silico molecular docking studies of alpha-amylase with phytocomponents from DCM extract. Among the top three compounds from virtual screening, induced fit docking studies revealed 2,5-bis(3,4-dimethoxyphenyl)-3,4-dimethyloxolane possessed better binding affinity when compared with the drug metformin. Conclusion: The obtained in vitro and in silico results suggest that all extracts of Myristica fragrans can be used successfully for the management of diabetes mellitus.Keywords: Myristica fragrans, Mace, Sequential extraction, Alpha-amylase, Molecular docking.

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Pengukuran Total Fenolik, Flavonoid, Aktivitas Antioksidan dan Antidiabetes Ekstrak Etil Asetat Daun Katemas (Euphorbia heterophylla, L.) Secara In Vitro dan In Silico Melalui Inhibisi Enzim α-Glukosidase

ALCHEMY Jurnal Penelitian Kimia ◽

10.20961/alchemy.16.2.40087.240-249 ◽

2020 ◽

Vol 16 (2) ◽

pp. 240

Author(s):

Rahmiwati Hilma ◽

Netti Gustina ◽

Jufrizal Syahri

Keyword(s):

Antioxidant Activity ◽

Molecular Docking ◽

Ethyl Acetate ◽

In Silico ◽

Ethyl Acetate Extract ◽

Dry Weight ◽

Antidiabetic Activity ◽

Total Phenolic ◽

Discovery Studio

Tujuan dari penelitian ini adalah untuk mengetahui aktivitas antioksidan dan antidiabetes ekstrak etil asetat daun katemas (Euphorbia heterophylla L.) secara in vitro dan in silico melalui inhibisi terhadap enzim α-glukosidase. Pada penelitian ini ekstraksi sampel dilakukan menggunakan maserasi bertingkat, dimulai dengan n-heksana, selanjutnya dengan etil asetat. Ekstrak etil asetat yang didapatkan dilakukan pengujian kuantitiatif total fenolik dan flavonoid. Uji aktivitas antioksidan terhadap ekstrak dilakukan menggunakan metode DPPH. Uji aktivitas antidiabetes terhadap ekstrak dilakukan secara in vitro dan in silico melalui inhibisi terhadap enzim α-glukosidase menggunakan akarbose sebagai standar. Uji aktivitas antidiabetes terhadap kandungan senyawa bioaktif ekstrak secara in silico atau molecular docking menggunakan software Discovery Studio 4.1. Hasil penelitian menunjukkan bahwa nilai total fenolik dari ekstrak adalah 4,24 mg GAE/g berat kering dan nilai flavonoid total adalah: 3,22 mg KE/g berat kering. Hasil uji aktivitas antioksidan ekstrak didapatkan nilai IC50 sebesar 37,56 µg/mL, digolongkan sebagai aktivitas antioksidan yang sangat kuat. Hasil uji aktivitas antidiabetes secara in vitro didapatkan nilai IC50 sebesar 138,63 µg/mL. Hasil molecular docking memperlihatkan bahwa senyawasenyawa aktif yang terdapat didalam ekstrak mampu membentuk ikatan hidrogen antara ligan dengan reseptor, tapi lebih sedikit jika dibandingkan dengan akarbose.Measurement of Total Phenolic, Flavonoids, Antioxidant and Antidiabetic Activity of Catemas Leaf Ethyl Acetate Extract (Euphorbia heterophylla L.) by In Vitro and In Silico through Enzim α-Glucosidase Inhibition. This study aims to determine the antidiabetic activity of katemas (Euphorbia heterophylla L.) ethyl acetate extract in vitro and in silico through inhibition of the αglucosidase enzyme. In this study, the sample extraction was carried out by multilevel maceration, starting with n-hexane, then with ethyl acetate. The ethyl acetate extract obtained was quantitatively tested by total phenolic and flavonoids. The antioxidant activity of the extract was tested using the DPPH method. The antidiabetic activity of the extract was examined through inhibiting the enzyme αglucosidase in vitro using a microplate reader and in silico (molecular docking) using Discovery Studio 4.1 software. The results showed that the total phenolic value of the extract was 4.24 mg GAE/g of dry weight, and the total flavonoid value was 3.22 mg KE/g of dry weight. Antioxidant activity test obtained IC50 of 37,56 µg/mL, classified as verry strong antioxidant. The in vitro antidiabetic test examined that IC50 is 138.63 µg/mL. The results of molecular docking showed that the active compounds in the extracts are able to form hydrogen bonds between ligand and receptor; however, the amount was less than the hydrogen bonds formed by acarbose.

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In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180220125406 ◽

2018 ◽

Vol 21 (3) ◽

pp. 215-221

Author(s):

Haroon Khan ◽

Muhammad Zafar ◽

Helena Den-Haan ◽

Horacio Perez-Sanchez ◽

Mohammad Amjad Kamal

Keyword(s):

In Silico ◽

Docking Studies ◽

In Vivo Studies ◽

In Vitro Assays ◽

Chronic Obstructive ◽

Lipoxygenase Inhibitors ◽

Lipoxygenase Inhibition ◽

In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

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Enzymatic Textile Dyes Decolorization by In vitro and In silico Studies

Recent Patents on Biotechnology ◽

10.2174/1872208313666190625123847 ◽

2019 ◽

Vol 13 (4) ◽

pp. 268-276

Author(s):

Sridevi Ayla ◽

Monika Kallubai ◽

Suvarnalatha Devi Pallipati ◽

Golla Narasimha

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Textile Dyes ◽

Crude Enzyme ◽

Eastern Ghats ◽

Textile Dye ◽

Phanerochaete Sordida ◽

Molecular Docking Studies ◽

In Silico Studies

Background:Laccase, a multicopper oxidoreductase (EC: 1.10.3.2), is a widely used enzyme in bioremediation of textile dye effluents. Fungal Laccase is preferably used as a remediating agent in the treatment and transformation of toxic organic pollutants. In this study, crude laccase from a basidiomycetes fungus, Phanerochaete sordida, was able to decolorize azo, antroquinone and indigoid dyes. In addition, interactions between dyes and enzyme were analysed using molecular docking studies.Methods:In this work, a white rot basidiomycete’s fungus, Phanerochaete sordida, was selected from forest soil isolates of Eastern Ghats, and Tirumala and lignolytic enzymes production was assayed after 7 days of incubation. The crude enzyme was checked for decolourisation of various synthetic textile dyes (Vat Brown, Acid Blue, Indigo, Reactive Blue and Reactive Black). Molecular docking studies were done using Autodock-4.2 to understand the interactions between dyes and enzymes.Results:Highest decolourisation efficiency was achieved with the crude enzyme in case of vat brown whereas the lowest decolourisation efficiency was achieved in Reactive blue decolourisation. Similar results were observed in their binding affinity with lignin peroxidase of Phanerochaete chrysosporium through molecular docking approach.Conclusion:Thus, experimental results and subsequent in silico validation involving an advanced remediation approach would be useful to reduce time and cost in other similar experiments.

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In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽

10.1186/s13099-021-00443-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Padikkamannil Abishad ◽

Pollumahanti Niveditha ◽

Varsha Unni ◽

Jess Vergis ◽

Nitin Vasantrao Kurkure ◽

...

Keyword(s):

Escherichia Coli ◽

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Antimicrobial Efficacy ◽

Drug Resistant ◽

Protein Motifs ◽

Phytochemical Compounds ◽

In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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In vitro and in silico studies of antioxidant activity of 2-thiazolylhydrazone derivatives

Journal of Molecular Graphics and Modelling ◽

10.1016/j.jmgm.2018.10.007 ◽

2019 ◽

Vol 86 ◽

pp. 106-112 ◽

Cited By ~ 3

Author(s):

Vinícius Gonçalves Maltarollo ◽

Marina Ferrara de Resende ◽

Thales Kronenberger ◽

Cleudiomar Inácio Lino ◽

Maria Clara Pinheiro Duarte Sampaio ◽

...

Keyword(s):

Antioxidant Activity ◽

In Silico ◽

In Silico Studies

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Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

Plants ◽

10.3390/plants11020208 ◽

2022 ◽

Vol 11 (2) ◽

pp. 208

Author(s):

Ahlam Elwekeel ◽

Dalia El Amir ◽

Enas I. A. Mohamed ◽

Elham Amin ◽

Marwa H. A. Hassan ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Docking Studies ◽

Antidiabetic Activity ◽

Flavonoid Glycosides ◽

Total Phenolic ◽

Cytotoxic Activities ◽

Alcoholic Extract ◽

Molecular Docking Study

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

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