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.

Monosubstituted Coumarins Inhibit Epinephrine-Induced Platelet Aggregation Antiplatelet Effect of Monosubstituted Coumarins

2021 ◽  
Vol 19 ◽  
Author(s):  
Fausto Alejandro Jiménez-Orozco ◽  
Sergio Galicia-Zapatero ◽  
Edgar López-López ◽  
José L. Medina-Franco ◽  
Fernando León Cedeño ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Drug Targets ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Human Platelets ◽  
In Silico Studies ◽  
Vitro Effect ◽  
Induced Aggregation

Aim: Evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various pro-aggregatory agonists, particularly by epinephrine. Background: The emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited. Objective: Establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Using in silico studies, suggest potential drug targets to which the molecules bind to produce antiplatelet effects. Methods: The platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 µM), collagen (2 µg / ml) or ADP (10 µM). The aggregation of controls platelets was considered 100% of the response for each pro-aggregatory agonists. Results: Eleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer. Conclusions : In silico studies suggest that most active molecules might have antagonistic interactions in the adrenoceptors α2 and β2. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

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.

Design, synthesis, in silico docking studies and biological evaluation of novel quinoxaline-hydrazide hydrazone-1,2,3-triazole hybrids as α-glucosidase inhibitors and antioxidants

2019 ◽  
Vol 43 (38) ◽  
pp. 15435-15452 ◽  
Author(s):  
Triloknadh Settypalli ◽  
Venkata Rao Chunduri ◽  
Aruna Kumari Maddineni ◽  
Nagaraju Begari ◽  
Rajasekhar Allagadda ◽  
...  
Keyword(s):  
In Silico ◽  
Antioxidant Activities ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Glucosidase Inhibitors

Novel quinoxaline-hydrazidehydrazone-1,2,3-triazole hybrids were synthesized, characterized and screened for α-glucosidase inhibitory and antioxidant activities.

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

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.

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Thiazole-Dihyrofuran Derivatives as Aromatase Inhibitors

2021 ◽  
pp. 105123
Author(s):  
Derya Osmaniye ◽  
Şennur Görgülü ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Aromatase Inhibitors ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies

scholarly journals Design, synthesis, in silico studies and in vitro evaluation of isatin-pyridine oximes hybrids as novel acetylcholinesterase reactivators

2021 ◽  
Vol 36 (1) ◽  
pp. 1370-1377
Author(s):  
Daniel A. S. Kitagawa ◽  
Rafael B. Rodrigues ◽  
Thiago N. Silva ◽  
Wellington V. dos Santos ◽  
Vinicius C. V. da Rocha ◽  
...  
Keyword(s):  
In Silico ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
In Silico Studies ◽  
Acetylcholinesterase Reactivators

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Triazoles as Anticancer Agents for Breast Cancer

2021 ◽  
pp. 131198
Author(s):  
Derya Osmaniye ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Sinem Ilgın ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies

scholarly journals The Bioactivity Prediction of Peptides from Tuna Skin Collagen Using Integrated Method Combining In Vitro and In Silico

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2739
Author(s):  
Liza Devita ◽  
Hanifah Nuryani Lioe ◽  
Mala Nurilmala ◽  
Maggy T. Suhartono
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Weight Fraction ◽  
Amino Acid Sequences ◽  
Skin Collagen ◽  
Dpph Method ◽  
Peptide Fractions

The hydrolysates and peptide fractions of bigeye tuna (Thunnus obesus) skin collagen have been successfully studied. The hydrolysates (HPA, HPN, HPS, HBA, HBN, HBS) were the result of the hydrolysis of collagen using alcalase, neutrase, and savinase. The peptide fractions (PPA, PPN, PPS, PBA, PBN, PBS) were the fractions obtained following ultrafiltration of the hydrolysates. The antioxidant activities of the hydrolysates and peptide fractions were studied using the DPPH method. The effects of collagen types, enzymes, and molecular sizes on the antioxidant activities were analyzed using profile plots analysis. The amino acid sequences of the peptides in the fraction with the highest antioxidant activity were analyzed using LC-MS/MS. Finally, their bioactivity and characteristics were studied using in silico analysis. The hydrolysates and peptide fractions provided antioxidant activity (6.17–135.40 µmol AAE/g protein). The lower molecular weight fraction had higher antioxidant activity. Collagen from pepsin treatment produced higher activity than that of bromelain treatment. The fraction from collagen hydrolysates by savinase treatment had the highest activity compared to neutrase and alcalase treatments. The peptides in the PBN and PPS fractions of <3 kDa had antidiabetic, antihypertensive and antioxidant activities. In conclusion, they have the potential to be used in food and health applications.

scholarly journals Novel substituted oxadiazole - piperazine derivatives as potential MAO inhibitors: Design, synthesis, in vitro and in silico studies

2022 ◽  
Vol 26(1) (26(1)) ◽  
pp. 1037-1044
Author(s):  
Harun USLU ◽  
Begüm Nurpelin SAĞLIK ◽  
Derya OSMANİYE ◽  
Kadriye BENKLİ
Keyword(s):  
In Silico ◽  
Mao Inhibitors ◽  
Design Synthesis ◽  
Piperazine Derivatives ◽  
In Silico Studies
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