scholarly journals 2-Hydroxy-5-(3,5,7-Trihydroxy-4-Oxo-4H-Chromen-2-yl)Phenyl (E)-3-(4-Hydroxy-3-Methoxyphenyl)Acrylate: Synthesis, In Silico Analysis and In Vitro Pharmacological Evaluation

Molbank ◽  
10.3390/m1258 ◽  
2021 ◽  
Vol 2021 (3) ◽  
pp. M1258
Author(s):  
Antonella Brizzi ◽  
Alfonso Trezza ◽  
Ottavia Spiga ◽  
Samuele Maramai ◽  
Francesco Scorzelli ◽  
...  
Keyword(s):  
In Silico ◽  
Parent Compound ◽  
Radical Scavenging ◽  
In Silico Analysis ◽  
Hybrid Compound ◽  
Elementary Analysis ◽  
In Silico Studies ◽  
Single Chemical ◽  
Cav1.2 Channels

Quercetin and ferulic acid are two phytochemicals extensively represented in the plant kingdom and daily consumed in considerable amounts through diets. Due to a common phenolic structure, these two molecules share several pharmacological properties, e.g., antioxidant and free radical scavenging, anti-cancer, anti-inflammatory, anti-arrhythmic, and vasorelaxant. The aim of the present work was the combination of the two molecules in a single chemical entity, conceivably endowed with more efficacious vasorelaxant activity. Preliminary in silico studies herein described suggested that the new hybrid compound bound spontaneously and with high affinity on the KCa1.1 channel. Thus, the synthesis of the 3′-ferulic ester derivative of quercetin was achieved and its structure confirmed by 1H- and 13C-NMR spectra, HSQC and HMBC experiments, mass spectrometry, and elementary analysis. The effect of the new hybrid compound on vascular KCa1.1 and CaV1.2 channels revealed a partial loss of the stimulatory activity that characterizes the parent compound quercetin. Therefore, further studies are necessary to identify a better strategy to improve the vascular properties of this flavonoid.

scholarly journals In Vivo, In Vitro and In Silico Studies of the Hybrid Compound AA3266, an Opioid Agonist/NK1R Antagonist with Selective Cytotoxicity

2020 ◽  
Vol 21 (20) ◽  
pp. 7738
Author(s):  
Joanna Matalińska ◽  
Piotr F. J. Lipiński ◽  
Piotr Kosson ◽  
Katarzyna Kosińska ◽  
Aleksandra Misicka
Keyword(s):  
In Silico ◽  
Molecular Orbital Calculations ◽  
Opioid Use ◽  
Opioid Agonist ◽  
Hybrid Compound ◽  
In Silico Studies ◽  
Neurokinin 1 ◽  
Dynamics Simulations

AA3266 is a hybrid compound consisting of opioid receptor agonist and neurokinin-1 receptor (NK1R) antagonist pharmacophores. It was designed with the desire to have an analgesic molecule with improved properties and auxiliary anticancer activity. Previously, the compound was found to exhibit high affinity for μ- and δ-opioid receptors, while moderate binding to NK1R. In the presented contribution, we report on a deeper investigation of this hybrid. In vivo, we have established that AA3266 has potent antinociceptive activity in acute pain model, comparable to that of morphine. Desirably, with prolonged administration, our hybrid induces less tolerance than morphine does. AA3266, contrary to morphine, does not cause development of constipation, which is one of the main undesirable effects of opioid use. In vitro, we have confirmed relatively strong cytotoxic activity on a few selected cancer cell lines, similar to or greater than that of a reference NK1R antagonist, aprepitant. Importantly, our compound affects normal cells to smaller extent what makes our compound more selective against cancer cells. In silico methods, including molecular docking, molecular dynamics simulations and fragment molecular orbital calculations, have been used to investigate the interactions of AA3266 with MOR and NK1R. Insights from these will guide structural optimization of opioid/antitachykinin hybrid compounds.

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

2020 ◽  
Vol 11 (2) ◽  
pp. 9629-9637
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Docking Studies ◽  
The Body ◽  
Insufficient Amount ◽  
In Silico Studies ◽  
Optimization Simulation ◽  
Alpha Glucosidase

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.

scholarly journals Evaluation and Elucidation of Bioactive Compounds from Leptogium rivurale Through in-vitro and in-silico Studies

2020 ◽  
Vol 2 (1) ◽  
pp. 10
Keyword(s):  
Aqueous Extract ◽  
In Silico ◽  
Methanol Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Docking Simulation ◽  
Bioactive Constituents ◽  
Drug Candidates ◽  
In Silico Studies

Leptoguium rivurale is a flooded jelly skin lichen, the surface of which becomes jelly when wet. It is a cyanolichen in which the photosynthetic partner is a cyanobacterium in the genus name Nostac. The present study was performed to investigate the bioactive constituents of Leptoguium rivurale. Samples were collected from forest regions of Kodaikanal. The collected Lichens were washed and dried and then extracted by using methanol and distilled water. Qualitative analysis of phytochemicals from the extracts showed the presence of carbohydrates, glycosides, phenols, terpenoids, saponins, and proteins. The amount of carbohydrates, phenols, and proteins was found to 350u/g and 380u/g, 200u/g, and 240u/g and 490u/g and 320u/g in aqueous and methanol extracts. The α-amylase enzyme inhibition assay ranged from 47.2% to 58.4% for methanol extract and from 35.12% to 51.1% for aqueous extract. The DPPH radical scavenging activity ranged from 27.6% to 49.8% for methanol extract and from 21.3% to 42.2% for aqueous extract. The anti-inflammatory activity ranged from 40.5% to 86.2% for methanol extract and from 49.4% to 79.2% for aqueous extract. Then the extract was given for GC-MS analysis. The molecules that were obtained in this analysis were used as ligands and in-silico molecular docking simulation was made using AutoDock software through which it was found that out of the docked ligands cyclohexanol and oxirane were the potential drug candidates.

In vitro and in silico studies of radical scavenging activity of salicylaldehyde benzoylhydrazones

2021 ◽  
pp. 131021
Author(s):  
Nadya G. Hristova-Avakumova ◽  
Evgenia P. Valcheva ◽  
O. Anastassova Neda ◽  
Boryana I. Nikolova-Mladenova ◽  
Liliya A. Atanasova ◽  
...  
Keyword(s):  
In Silico ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Scavenging Activity ◽  
In Silico Studies

Isothymusin, a Potential Inhibitor of Cancer Cell Proliferation: An In Silico and In Vitro Investigation

2020 ◽  
Vol 20 (21) ◽  
pp. 1898-1909
Author(s):  
Shilpi Singh ◽  
Priyanka Kumari ◽  
Yusuf Hussain ◽  
Suaib Luqman ◽  
Abha Meena ◽  
...  
Keyword(s):  
Cancer Cell ◽  
In Silico ◽  
Radical Scavenging ◽  
Redox Activity ◽  
Breast Adenocarcinoma ◽  
Ocimum Sanctum ◽  
Breast Cancer Cell Lines ◽  
In Vitro Investigation ◽  
In Silico Studies

Background: Since centuries plant-based compounds are known for the treatment of cancer in both traditional and contemporary medicine. The problems like target non-specificity and toxicity are well-known regarding anticancer drugs. Therefore, target specific search of novel entities is constant. Isothymusin is a dimethoxy, trihydroxy flavone present in plants like Ocimum sanctum, and Limnophilla geoffrayi. There are limited reports available on the anticancer potential of isothymusin. Objectives: The effects of isothymusin on redox status, cell cytotoxicity, and targets involved in the promotion and progression of the cancer cells have been investigated. Methods: Antiproliferative efficacy was evaluated by MTT, Neutral Red Uptake, and Sulforhodamine-B assays. The spectrophotometric methods were adopted to study the effect against selected targets. Redox activity was assessed by in vitro antioxidant assays and the interaction study, ADMET profiling, and toxicity assessments were done in silico. Results: Isothymusin scavenges the radicals, i.e., DPPH and nitric oxide with moderate ferric reducing potential. It affected the proliferation of leukemia, colon, skin, and breast cancer cell lines by more than 50% but moderately affected prostate, kidney, lung, hepatic, and breast adenocarcinoma (up to 48%). Isothymusin inhibited the enzymes associated with the promotion stage of cancer, including cycloxygenase- 2 and lipoxygenase-5. Additionally, it also inhibited the activity of proliferation markers like cathepsin- D, dihydrofolate reductase, hyaluronidase, and ornithine-decarboxylase. Besides, in silico studies supported the in vitro enzyme inhibition assays outcome. Toxicity studies showed promising results of chemical descriptors and non-skin-irritant, moderate ocular-irritancy, and in vitro Ames test confirmed non-mutagenic nature. Conclusion: Isothymusin showed radical scavenging and anti-proliferative activities, which may be taken up as a phytochemical lead for the synthesis of analogues possessing enhanced anticancer potential.

Structure-Activity Relationship Study of an Alkynylphosphonate and a Vynilphosphonate Analogues of Calcitriol

2020 ◽  
Vol 16 ◽  
Author(s):  
Silvina Mariela Grioli ◽  
Eliana Noelia Alonso ◽  
Evangelina Mascaró ◽  
Santiago Armando Stabile ◽  
María Julia Ferronato ◽  
...  
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Rational Design ◽  
Parent Compound ◽  
In Vitro Assays ◽  
Antitumoral Activity ◽  
Lateral Side ◽  
Antitumor Effects ◽  
In Silico Studies

Background: 1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different can-cer cell lines but its hypercalcemic effects have severely hampered its therapeutic application. Therefore, it is important todevelop synthetic calcitriol analogues that retain or even increase its antitumoral effects and lack hypercalcemic activity. Based on previous evidence of the potent antitumor effects of the synthetic alkynylphosphonate EM1 analogue, we have now synthesized a derivative called SG. Objective: The aim of the present work is to evaluate the calcemic activity and the antitumor effect of SG, comparing these effects with those exerted by calcitriol and with those previously published for EM1. In addition, we propose to analyse by in silico studies the chemical structure-biological function relationship of these molecules. Methods: We performed the synthesis of vinylphosphonate SG analogue; in vitro assays on different cancer cell lines; in vivo assays on mice; and in silico assays applying computational molecular modelling. Results: The SG compound lacks hypercalcemic activity, similar to the parent compound EM1. However, the antitumor ac-tivity was blunted, as no antiproliferative or antimigratory effects were observed. By in silico assays, we demostrated that SG analogue has lower affinity for the VDR-ligand binding domain than EM1 compound, due to lack of interaction with the important residues His305 and His397. Conclusion: These results demonstrate that chemical modification in the lateral side chain of the SG analogue affects the antitumoral activity observed previously for EM1 but does not affect the calcemic activity. These results contribute to the rational design and synthesis of novel calcitriol analogues.

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

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.

scholarly journals 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 ◽  
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.

scholarly journals Phycocyanin Extracted from Oscillatoria minima Shows Antimicrobial, Algicidal, and Antiradical Activities: In silico and In vitro Analysis

2020 ◽  
Vol 19 (3) ◽  
pp. 240-253 ◽  
Author(s):  
Vaishali C. Venugopal ◽  
Abhimanyu Thakur ◽  
Latha K. Chennabasappa ◽  
Gaurav Mishra ◽  
Kunal Singh ◽  
...  
Keyword(s):  
In Silico ◽  
Radical Scavenging ◽  
Gel Filtration ◽  
Qualitative Evaluation ◽  
Exchange Chromatography ◽  
Alternative Source ◽  
Ammonium Sulphate Precipitation ◽  
In Silico Studies ◽  
Vitro Analysis

Background: Phycocyanin is an algae-derived protein, which binds to pigment for harvesting light. It has been reported in various different species, including that of red algae, dinoflagellates, and cryptophyta. Importantly, phycocyanin has enormous applications, including cosmetic colorant, food additive, biotechnology, diagnostics, fluorescence detection probe, an anticancer agent, anti-inflammatory, immune enhancer, etc. In addition, several different algae were utilized for the isolation of cyano-phycocyanin (C-PC), but most of the purification methods consist of several steps of crude extraction. Aim: To isolate C-PC from a new source of microalgae with better purity level and to evaluate its antimicrobial, algicidal, and antiradical activities. Methods: Biological activity, permeability, pharmacokinetics, and toxicity profile of C-PC were predicted by in silico studies. C-PC was purified and isolated by using ammonium sulphate precipitation, ion-exchange chromatography and gel-filtration chromatography. C-PC was characterized by SDS-PAGE and elution profile (purity ratio) analysis. Antimicrobial and algicial activities of C-PC were evaluated by the microtitre plate based assays. Antiradical activity of C-PC was evaluated by DPPH- and ABTS*+ radical scavenging assays. Conclusion: C-PC was extracted from Oscillatoria minima for the first time, followed by its quantitative as well qualitative evaluation, indicating a new alternative source of this important protein. Furthermore, the antimicrobial, algicidal, and antiradical activities of the isolated C-PC extract have been demonstrated by both in silico as well as in vitro methods.

scholarly journals Evaluation of Antioxidants, Antidiabetic, Antiinflammatory Active Compounds from Leptogium rivurale Through In-Vitro and In-Silico Studies

2021 ◽  
Vol 11 (4) ◽  
pp. 4192-4200
Keyword(s):  
Aqueous Extract ◽  
In Silico ◽  
Methanol Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Docking Simulation ◽  
Drug Candidates ◽  
Ms Analysis ◽  
In Silico Studies

Leptogium rivurale is a flooded jelly skin lichen as the surface becomes jelly on wet. It is a cyanolichen with a cyanobacterium Nostoc. In this present study, Leptoguium rivurale were collected from Kodaikanal and extracted using methanol and distilled water. Qualitative analysis of phytochemicals from the extracts showed the presence of carbohydrates, glycosides, phenols, terpenoids, saponins, and proteins. The methanol extract was found to inhibit the α-amylase enzyme activity better than aqueous extract. The methanol extract was found to have better DPPH radical scavenging activity and anti-inflammatory activity than aqueous extract. Then the extract was subjected to GC-MS analysis. The molecules obtained through GC-MS analysis were subjected to in-silico molecular docking simulation using AutoDock software. Cyclohexanol and oxirane were the potential drug candidates identified.

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