scholarly journals 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

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.

scholarly journals Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

2021 ◽  
Vol 17 ◽  
Author(s):  
Thiago M. de Aquino ◽  
Paulo H. B. França ◽  
Érica E. E. S. Rodrigues ◽  
Igor J. S. Nascimento ◽  
Paulo F. S. Santos-Júnior ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Trypanothione Reductase ◽  
Aromatic Substituent ◽  
In Silico Studies ◽  
Ic50 Values ◽  
The Impact

Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objective: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds. Method: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. Result: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

Promising antileishmanial activity of novel imidazole antifungal drug luliconazole against Leishmania major: In vitro and in silico studies

2018 ◽  
Vol 14 ◽  
pp. 260-265 ◽  
Author(s):  
Azar Shokri ◽  
Mahdi Abastabar ◽  
Masoud Keighobadi ◽  
Saeed Emami ◽  
Mahdi Fakhar ◽  
...  
Keyword(s):  
In Silico ◽  
Leishmania Major ◽  
Antifungal Drug ◽  
Antileishmanial Activity ◽  
In Silico Studies

scholarly journals Selected Derivatives of Erythromycin B-In Silico and Anti-Malarial Studies

Materials ◽  
2021 ◽  
Vol 14 (22) ◽  
pp. 6980
Author(s):  
Pranab K. Bhadra ◽  
Rachael N. Magwaza ◽  
Niroshini Nirmalan ◽  
Sally Freeman ◽  
Jill Barber ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Bacterial Agent ◽  
Ic50 Values ◽  
Exit Tunnel ◽  
Erythromycin A ◽  
Erythronolide B ◽  
In Silico Molecular Docking ◽  
Derivatives Of

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.

The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

2020 ◽  
Vol 10 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Essential Oils ◽  
In Silico ◽  
Candida Rugosa ◽  
Inhibitory Effect ◽  
Mentha Piperita ◽  
Inhibition Mechanism ◽  
Syzygium Aromaticum ◽  
In Silico Studies

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.

scholarly journals Interaction of Ligands for PET with the Dopamine D3 Receptor: In Silico and In Vitro Methods

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 529
Author(s):  
Chia-Ju Hsieh ◽  
Aladdin Riad ◽  
Ji Youn Lee ◽  
Kristoffer Sahlholm ◽  
Kuiying Xu ◽  
...  
Keyword(s):  
In Silico ◽  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
In Silico Studies ◽  
Ic50 Values ◽  
Pet Radiotracers ◽  
Dopamine D3 ◽  
Competition Assays

[18F]Fallypride and [18F]Fluortriopride (FTP) are two different PET radiotracers that bind with sub-nanomolar affinity to the dopamine D3 receptor (D3R). In spite of their similar D3 affinities, the two PET ligands display very different properties for labeling the D3R in vivo: [18F]Fallypride is capable of binding to D3R under “baseline” conditions, whereas [18F]FTP requires the depletion of synaptic dopamine in order to image the receptor in vivo. These data suggest that [18F]Fallypride is able to compete with synaptic dopamine for binding to the D3R, whereas [18F]FTP is not. The goal of this study was to conduct a series of docking and molecular dynamic simulation studies to identify differences in the ability of each molecule to interact with the D3R that could explain these differences with respect to competition with synaptic dopamine. Competition studies measuring the ability of each ligand to compete with dopamine in the β-arrestin assay were also conducted. The results of the in silico studies indicate that FTP has a weaker interaction with the orthosteric binding site of the D3R versus that of Fallypride. The results of the in silico studies were also consistent with the IC50 values of each compound in the dopamine β-arrestin competition assays. The results of this study indicate that in silico methods may be able to predict the ability of a small molecule to compete with synaptic dopamine for binding to the D3R.

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

Biomedicines ◽  
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.

Essential oil from Galls formed on leaves of Pistacia atlantica Desf.: New in-vitro and in-silico studies of anti-inflammatory activities

2022 ◽  
Vol 144 ◽  
pp. 464-470
Author(s):  
Sifi Ibrahim ◽  
Yousfi Mohamed ◽  
Benarous Khedidja ◽  
Dzoyem Jean Paul ◽  
Eloff Jacobus Nicolaas
Keyword(s):  
Essential Oil ◽  
In Silico ◽  
Pistacia Atlantica ◽  
In Silico Studies ◽  
Anti Inflammatory

The inhibitory Effects of Some Artificial Food Colorings on α-amylase and α-glucosidase: In Vitro and In Silico Studies

2021 ◽  
Vol 17 ◽  
Author(s):  
Reguia Mahfoudi ◽  
Amar Djeridane ◽  
Djilali Tahri ◽  
Mohamed Yousfi
Keyword(s):  
In Silico ◽  
Hydrophobic Interactions ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Qsar Study ◽  
Molegro Virtual Docker ◽  
Artificial Food ◽  
In Silico Studies ◽  
Ic50 Values

Background: Inhibition of α-amylase and α-glucosidase is considered as an important therapeutic target to manage type 2 diabetes mellitus (T2DM), reducing postprandial hyperglycemia (PPHG). Objective: The present work explored the antidiabetic activities of five artificial food colorings by α-amylase and α-glucosidase enzyme inhibition in vitro and in Silico. Methods: In this study, inhibition of α-amylase and α-glucosidase were evaluated. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (food colorings) was followed by QSAR and molecular docking studies. Results: The in vitro results obtained show that the blue patent (SIN131) exhibited more potent inhibition with IC50 values of 0.03± 0.01 mM and 0.014±0.001 mM against α-amylase and α-glucosidase inhibition respectively compared to acarbose. The QSAR study found a strong correlation between IC50 values with four molecular descriptors. This linear regression confirms that a strong polarity (Apol) and a low hydrophobia (ALogP) favor the inhibitory effect of these colorings toward both enzymes. Also, a negative role of the number of heavy atoms has been demonstrated in the phenomenon of inhibition of this enzyme. Finally, the descriptor εlumo (electronic affinity) plays a crucial role on the inhibitory power of these dyes toward both enzymes by electron transfer. The virtual screening of the inhibition of α-amylase and α-glucosidase by these colorings, using Molegro Virtual Docker (MVD), allowed us to obtain stable complexes with interaction energies resulting from the place of hydrogen bonds and several hydrophobic interactions. However, the sulfonate groups of these colorings can be the major factors in the inhibition of these enzymes. On the other hand, Rerank Score with the pose are perfectly correlated (R2> 0.76) to the inhibitory activity of these food colorings measured experimentally. Conclusion: The present study suggests that the Blue Patent V (SIN131) effectively act as α-amylase and α-glucosidase inhibitor leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels.

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

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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