A Simplistic Approach for Preparation of Alkylidenemalononitrile Derivatives: Characterization, In silico Studies, Quantum Chemical Evaluation, Molecular Docking, and In vitro Biological Activity Evaluation

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

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

Biomedicines ◽

10.3390/biomedicines9101380 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1380

Author(s):

Johanis Wairata ◽

Edwin Risky Sukandar ◽

Arif Fadlan ◽

Adi Setyo Purnomo ◽

Muhammad Taher ◽

...

Keyword(s):

Antioxidant Activity ◽

Molecular Docking ◽

In Silico ◽

Stem Bark ◽

Docking Studies ◽

Antidiabetic Activity ◽

In Silico Studies ◽

Dehydrogenase Enzyme ◽

Ch2cl2 Extract

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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3-Methoxycarpachromene and Masticadienonic Acid as New Target Inhibitors from Pistacia atlantica Leaves against Trypanothione Reductase of Leishmania Parasites: In Vitro and In Silico Studies

10.20944/preprints202105.0348.v1 ◽

2021 ◽

Author(s):

Saarra Maamri ◽

Khedidja Benarous ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

In Silico ◽

Leishmania Major ◽

Trypanothione Reductase ◽

Binding Modes ◽

Pistacia Atlantica ◽

In Silico Studies ◽

Ic50 Values ◽

Leishmania Parasites

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

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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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Lepidine B & E as New Target Inhibitors from Lepidium Sativum Seeds Against Four Enzymes of the Pathogen Candida albicans: In Vitro and In Silico Studies

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190415141520 ◽

2020 ◽

Vol 20 (1) ◽

pp. 127-138

Author(s):

Safia Gacemi ◽

Khedidja Benarous ◽

Santiago Imperial ◽

Mohamed Yousfi

Keyword(s):

Candida Albicans ◽

Molecular Docking ◽

Antifungal Activity ◽

In Silico ◽

Candida Rugosa ◽

Antifungal Drugs ◽

Yeast Cells ◽

Lepidium Sativum ◽

In Silico Studies

Background and Objective: The present paper aims to study the inhibition of Candida albicans growth as candidiasis treatment, using seeds of Lepidium sativum as source. Methods: In vitro assays were carried out on the antifungal activity of three kinds of extracts from L. sativum seeds against four strains of C. albicans, then testing the same phytochemicals on the inhibition of Lipase (LCR). A new in silico study was achieved using molecular docking, with Autodock vina program, to find binding affinity of two important and major lepidine alkaloids (lepidine E and B) towards the four enzymes secreted by C. albicans as target drugs, responsible of vitality and virulence of this yeast cells: Lipase, Serine/threonine phosphatase, Phosphomannose isomerase and Sterol 14-alpha demethylase (CYP51). Results: The results of the microdillution assay show that the hexanic and alkaloidal extracts have an antifungal activity with MICs: 2.25 mg/ml and 4.5mg/ml, respectively. However, Candida rugosa lipase assay gives a remarkable IC50 values for the hexanic extract (1.42± 0.04 mg/ml) followed by 1.7± 0.1 and 2.29 ± 0.09 mg/ml of ethyl acetate and alkaloidal extracts respectively. The molecular docking confirms a significant correlation between C. albicans growth and inhibition of crucial enzymes involved in the invasion mechanism and cellular metabolisms, for the first time there were an interesting and new positive results on binding modes of lepidine E and B on the four studied enzymes. Conclusion: Through this work, we propose Lepidine B & E as potent antifungal drugs.

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In vitro and in silico studies of two 1,4-naphthoquinones and their topical formulation in bigels

Current Drug Delivery ◽

10.2174/1567201818666210618111118 ◽

2021 ◽

Vol 18 ◽

Author(s):

Imen Khelifi ◽

Audrey Tourrette ◽

Daycem Khelifi ◽

Thomas Efferth ◽

El Akrem Hayouni ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Water Solubility ◽

Biological Activities ◽

Binding Energies ◽

Topical Formulation ◽

Plant Metabolites ◽

Secondary Plant Metabolites ◽

In Silico Studies

Background: 1,4-Naphthoquinones (1,4-NQs) are secondary plant metabolites with numerous biological activities. 1,4-NQs display low water solubility and poor bioavailability. Bigels are a new technology with great potential, which are designated as drug delivery systems. Biphasic bigels consisting of solid and liquid components represent suitable formulations improving the diffusion and bioavailability of NQs into the skin. Objective: We evaluated the in silico and in vitro activity of 5,8-dihydroxy-1,4-naphthoquinone (M1) and 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M2) on elastase and assessed their cytotoxicity towards COLO38 melanoma cells. The 1,4-NQs were loaded into bigels for topical application. Methods: Molecular docking was performed, and cytotoxicity was evaluated on COLO38 cells using the resazurin assay. M1 and M2 were separately incorporated into bigels consisting of hydrogel organogel with sweet almond oil as a non-polar solvent and span 65 as organogelator. Their rheological behavior and microscopic properties were characterized. The diffusion kinetics and permeation of 1,4-NQs from bigels were studied by a paddle-over-extraction cell and a “Franz cell” in vitro permeation model. Results: Molecular docking data predicted high interactions between elastase and ligands. Hydrogen bonds to LYS233 were observed for M1, M2, and phosphoramidon (positive control). The average binding energies were -8.5 and -9.7 kcal/mol for M1 and M2 and -12.6 kcal/mol for phosphoramidon. M1 and M2 inhibited the elastase activity by 58.9 and 56.6%, respectively. M1 and M2 were cytotoxic towards COLO38 cells (IC50: 2.6 and 9.8 µM) y. The M1 release from bigels was faster and more efficient than that of M2. Conclusion: M1 and M2 are promising for skin disease treatment. Biphasic organogel-hydrogel bigels are efficient and safe formulations to overcome their low bioavailability.

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Sterols from Jatropha tanjorensis leaves exhibit anti-inflammatory potential: in vitro and in silico studies

Bulletin of the National Research Centre ◽

10.1186/s42269-021-00658-z ◽

2021 ◽

Vol 45 (1) ◽

Author(s):

Damilola Alex Omoboyowa

Keyword(s):

Molecular Docking ◽

In Silico ◽

Diclofenac Sodium ◽

Ethanol Extract ◽

Pharmacokinetic Profile ◽

Gas Chromatography Mass Spectrometry ◽

Toxicity Screening ◽

In Silico Studies ◽

Anti Inflammatory

Abstract Background Inflammation has continued to raise global challenges and Jatropha tanrogenesis (JT) is used traditionally for its management. In this study, the in silico and in vitro anti-inflammatory potential of bioactive sterols were investigated. The active compounds of ethanol extract of JT leaves were identified using Gas chromatography-mass spectrometry (GC.MS) followed by molecular docking against COX-1 and COX-2 using maestro Schrödinger and pharmacokinetic profile prediction using webserver tools. The in vitro anti-inflammatory and anti-oxidantive potentials were investigated using standard protocols. Results GC–MS analysis of ethanol extract of JT leaves revealed the presence of eight (8) compounds, the molecular docking analysis of these compounds demonstrated varying degrees of binding affinities against the target proteins. The extract exhibit concentration dependent anti-oxidant activity with IC50 of 106.383 and 6.00 Fe2+E/g for DPPH and FRAP respectively. The extract showed significant (P < 0.05) reduction in percentage inhibition of hemolysis at 200 µg/ml while non-significant (P > 0.05) increase was observed at 600 and 1000 µg/ml compared to 200 µg/ml of diclofenac sodium. At lower concentration of 25 and 50 µg/ml, percentage inhibition of albumin denaturation was significantly (P < 0.05) higher compared to 200 µg/ml of diclofenac sodium. Drug likeness prediction and ADME/toxicity screening showed that the bioactive compounds possess no side effects. Conclusion The results obtained in this study suggested that, JT leaves possess anti-inflammatory activity and could be used as a source of new drug.

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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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