In Silico Analysis and Molecular Docking Studies of Plumbagin and Piperine Ligands as Potential Inhibitors of Alpha-Glucosidase Receptor

In ’today’s generation, Diabetes mellitus is a very common lifestyle-based disease in which an insufficient amount of insulin is produced, which results in a rise of glucose level in the body with frequent urination and patient feels thirsty and hungry. In our present work, we have used the alpha-glucosidase receptor against the natural plant product as a ligand for docking studies. For this in silico studies, various online tools, databases, and software were used. The proposed approaches were PDB, Molinspiration, Chemsketch, PyRx software, and many more. The binding scores were retrieved by PyRx software and no tumorigenicity, mutagenicity was there, and all parameters were in the desired range. The compounds used as ligands have shown energy minimization up to -6.7 to -8.7 kcal and can be further used as optimization, simulation, and in vitro and in vivo experimental validation.

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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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New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180326152726 ◽

2018 ◽

Vol 16 (1) ◽

pp. 82-92 ◽

Cited By ~ 1

Author(s):

Ahmet Özdemir ◽

Belgin Sever ◽

Mehlika Dilek Altıntop

Keyword(s):

In Silico ◽

Fungal Infections ◽

Computational Study ◽

Docking Studies ◽

In Vivo Studies ◽

Heme Group ◽

In Silico Studies ◽

Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

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Synthesis, In-vitro Antioxidant, Anti-diabetic Evaluation and Docking Studies of Newly Synthesized Benzoxazole Derivatives

Trends in Sciences ◽

10.48048/tis.2021.35 ◽

2021 ◽

Vol 18 (21) ◽

pp. 35

Author(s):

Manuel Rodrigues ◽

Basavaraju Bennehalli ◽

Vagdevi Hosadu Manjappaiah ◽

Shruthi Anantha

Keyword(s):

In Silico ◽

Reducing Power ◽

Docking Studies ◽

Alpha Amylase ◽

Dpph Assay ◽

Analytical Instruments ◽

In Silico Studies ◽

Total Antioxidant ◽

Alpha Glucosidase

In the present study, a set of different benzoxazole derivatives has been synthesized from ethyl acetoacetate, ethoxymethylene malononitrile, NaNO2, and organic acids. Analytical instruments like proton NMR (1H), carbon NMR (13C), infrared spectroscopy (IR), and LC-MS mass spectrometry were used for structural characterization. Synthesized molecules were evaluated for In-vitro antioxidant property (DPPH assay, Total antioxidant & reducing power method) and anti-diabetic property (alpha-amylase & alpha-glucosidase assay). In silico, studies against Human pancreatic alpha-amylase (PDB ID: 3BAW) have been carried out to get the binding approach of the ligand towards the protein. The results demonstrated that compounds namely 5b, 6b, 3b and 4b had potent antioxidant and anti-diabetic activity compared with ascorbic acid and acarbose. HIGHLIGHTS Anti-oxidant (DPPH assay, Total antioxidant and Reducing power) and Anti-diabetic (alpha-amylase & alpha-glucosidase assay) activities performed for synthesized molecules Sulfonamide substitutions are more potent towards biological activities In silico docking studies correlate with in vitro studies The small three-dimensional, stable structure and its ability to form hydrogen bonding the molecules show good activity towards antioxidant and anti-diabetic GRAPHICAL ABSTRACT

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In silico, in-vitro and in vivo screening of biological activities of citral

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000625 ◽

2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Shagufta Habib ◽

Pawan Gupta ◽

Sana Shafi Bhat ◽

Jeena Gupta

Keyword(s):

In Silico ◽

Biological Activities ◽

In Silico Analysis ◽

Biological Properties ◽

Docking Studies ◽

Industrial Applications ◽

Yeast Cells ◽

Cam Assay

Abstract. Citral, one of the main components of lemongrass oil (65–85%), is known to possess various medicinal properties like enhancing skin health and vision-improvement. It also acts as flavoring agent, used in perfumes and skin care products. The objective of this work was to elucidate the biological properties of citral at molecular level using an integrated in silico, in vitro and in vivo approaches. To elucidate this in silico molecular docking studies were performed with in vitro validation by DPPH scavenging activity, MTT assays, enzymatic assays and Chorio Allantoic Membrane (CAM) assay. The in silico analysis demonstrated the potential binding of citral with PPARγ ligand binding domain and vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2). Citral is already a proven anti-oxidant which is further confirmed by increased DPPH inhibition with increased citral concentration (IC50: 6.9 ± 1.68 μg/ml, p < 0.05). The results demonstrated that citral protect yeast cells from cytotoxic effects of hydrogen peroxide and also increase the activities of antioxidant enzymes like GST, SOD and LPO. It was also demonstrated to be cytotoxic to cancerous HeLa cells (IC50: 3.9 ± 0.38 μM, p < 0.01) and was found anti-angiogenic by CAM assay. This study highlights many important pharmaceutical properties of citral which can be explored further to increase its industrial applications.

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Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and in silico Studies

Current Pharmaceutical Design ◽

10.2174/1381612827666211116102031 ◽

2021 ◽

Vol 27 ◽

Author(s):

Bharti Rajesh Kumar Shyamlal ◽

Manas Mathur ◽

Dharmendra K. Yadav ◽

Irina V. Mashevskaya ◽

Mohamed El-Shazly ◽

...

Keyword(s):

Platelet Aggregation ◽

In Silico ◽

Antioxidant Activities ◽

In Silico Analysis ◽

Antiplatelet Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Design Synthesis ◽

In Silico Studies

Background: Several natural/synthetic molecules having structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of molecular framework, have been explored for their antioxidant or antiplatelet activities. Introduction: Based on literature, a new prototype i.e., 3-phenyl-1H-isochromen-1-ones based compounds have been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues and performing in vitro antioxidant as well as AA-induced antiplatelet activities and then, identification of potent compounds by SAR and molecular docking studies. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-folds to 16-folds highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost, all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship and in silico studies of pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

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Unraveling the Antioxidant, Binding and Health-Protecting Properties of Phenolic Compounds of Beers with Main Human Serum Proteins: In Vitro and In Silico Approaches

Molecules ◽

10.3390/molecules25214962 ◽

2020 ◽

Vol 25 (21) ◽

pp. 4962

Author(s):

Raja Mohamed Beema Shafreen ◽

Selvaraj Alagu Lakshmi ◽

Shunmugiah Karutha Pandian ◽

Yong Seo Park ◽

Young Mo Kim ◽

...

Keyword(s):

Human Serum ◽

In Silico ◽

Serum Proteins ◽

In Silico Analysis ◽

Cardiovascular Effects ◽

In Vivo Studies ◽

In Silico Studies ◽

Human Serum Proteins

Our recently published in vivo studies and growing evidence suggest that moderate consumption of beer possesses several health benefits, including antioxidant and cardiovascular effects. Although beer contains phenolic acids and flavonoids as the major composition, and upon consumption, the levels of major components increase in the blood, there is no report on how these beer components interact with main human serum proteins. Thus, to address the interaction potential between beer components and human serum proteins, the present study primarily aims to investigate the components of beer from different industrial sources as well as their mode of interaction through in silico analysis. The contents of the bioactive compounds, antioxidant capacities and their influence on binding properties of the main serum proteins in human metabolism (human serum albumin (HSA), plasma circulation fibrinogen (PCF), C-reactive protein (CRP) and glutathione peroxidase 3 (GPX3)) were studied. In vitro and in silico studies indicated that phenolic substances presented in beer interact with the key regions of the proteins to enhance their antioxidant and health properties. We hypothesize that moderate consumption of beer could be beneficial for patients suffering from coronary artery disease (CAD) and other health advantages by regulating the serum proteins.

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Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612826666201112143230 ◽

2020 ◽

Vol 26 ◽

Author(s):

John Chen ◽

Andrew Martin ◽

Warren H. Finlay

Keyword(s):

Drug Delivery ◽

In Silico ◽

Local Drug Delivery ◽

In Vivo Studies ◽

Intranasal Drug Delivery ◽

Nasal Sprays ◽

In Silico Studies ◽

Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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In Silico Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692118666200106113610 ◽

2020 ◽

Vol 17 (2) ◽

pp. 125-132

Author(s):

Marjanu Hikmah Elias ◽

Noraziah Nordin ◽

Nazefah Abdul Hamid

Keyword(s):

Targeted Therapy ◽

In Silico ◽

Structure Prediction ◽

Tertiary Structure ◽

Target Prediction ◽

In Silico Analysis ◽

Microrna Target ◽

Good Target

Background: Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. Methods: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. Results: In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR- 8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML.

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In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity

Journal of Fungi ◽

10.3390/jof7060439 ◽

2021 ◽

Vol 7 (6) ◽

pp. 439

Author(s):

Tecla Ciociola ◽

Walter Magliani ◽

Tiziano De Simone ◽

Thelma A. Pertinhez ◽

Stefania Conti ◽

...

Keyword(s):

In Silico ◽

Mammalian Cells ◽

Galleria Mellonella ◽

Ex Vivo ◽

Consensus Sequence ◽

In Silico Analysis ◽

Significant Activity ◽

Synthetic Antibody

It has been previously demonstrated that synthetic antibody-derived peptides could exert a significant activity in vitro, ex vivo, and/or in vivo against microorganisms and viruses, as well as immunomodulatory effects through the activation of immune cells. Based on the sequence of previously described antibody-derived peptides with recognized antifungal activity, an in silico analysis was conducted to identify novel antifungal candidates. The present study analyzed the candidacidal and structural properties of in silico designed peptides (ISDPs) derived by amino acid substitutions of the parent peptide KKVTMTCSAS. ISDPs proved to be more active in vitro than the parent peptide and all proved to be therapeutic in Galleria mellonella candidal infection, without showing toxic effects on mammalian cells. ISDPs were studied by circular dichroism spectroscopy, demonstrating different structural organization. These results allowed to validate a consensus sequence for the parent peptide KKVTMTCSAS that may be useful in the development of novel antimicrobial molecules.

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