scholarly journals Design and Synthesis of Novel Thiazolo[5,4-d]Pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 657
Author(s):  
Flavia Varano ◽  
Daniela Catarzi ◽  
Erica Vigiani ◽  
Diego Dal Ben ◽  
Michela Buccioni ◽  
...  
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Docking Studies ◽  
In Vivo Studies ◽  
A2a Receptors ◽  
Design And Synthesis ◽  
Sucrose Preference Test ◽  
New Compounds

New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18–19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline.

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.

scholarly journals Effect of Harmine against Parkinson’s Disease Protein (PARK7) through Molecular Docking Studies

2021 ◽  
Vol 9 (VI) ◽  
pp. 5479-5485
Author(s):  
Love Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Receptor Protein ◽  
Unknown Etiology

Parkinson’s disease (PD) is a common known neurodegenerative disorder with unknown etiology. It was estimated about 0.3% prevalence in the U.S population and enhance to 4 to 5% in older than 85 years. All studies were depending on the molecular docking where all ligands and protein PARK7 (PDB ID: 2RK3) were interacted by docked process. Some natural compounds was selected such as Harmine, Alloxan, Alpha spinasterol, Myrcene, and Vasicinone and PARK7 (PDB ID: 2RK3) protein. According to the PyRx and SWISS ADME result, Harmine was the only ligand which was showing minimum binding affinity. AutoDock Vina software was used for docking process between ligand (Harmine) and receptor protein PARK7 (PDB ID: 2RK3). The result was visualized under PyMol. Harmine was inhibiting the activity of PARK7 (PDB ID: 2RK3) and it may be used for the treatment of PD in future prospect after its in vitro and in vivo studies.

The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of In vitro and In vivo studies

2003 ◽  
Vol 13 (22) ◽  
pp. 4077-4080 ◽  
Author(s):  
Moorthy S.S. Palanki ◽  
Paul E. Erdman ◽  
Minghuan Ren ◽  
Mark Suto ◽  
Brydon L. Bennett ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
In Vivo Studies ◽  
Design And Synthesis ◽  
Orally Active

scholarly journals In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4018
Author(s):  
Paula P. de Paiva ◽  
Julia H. B. Nunes ◽  
Fabiana R. Nonato ◽  
Ana L. T. G. Ruiz ◽  
Rafael R. T. Zafred ◽  
...  
Keyword(s):  
Human Tumor ◽  
Antitumor Agent ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Myeloperoxidase Activity ◽  
Aerial Parts ◽  
M Phase ◽  
Anti Inflammatory

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine’s binding site on β-tubulin were performed, suggesting (−)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

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

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
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.

Nanocarriers for Vaccine and Gene Delivery Application

2018 ◽  
pp. 381-414 ◽  
Author(s):  
Behiye Şenel ◽  
Gülay Büyükköroğlu
Keyword(s):  
Genetic Material ◽  
Biological Properties ◽  
Target Site ◽  
Inorganic Nanoparticles ◽  
In Vivo Studies ◽  
Polymeric Systems ◽  
Design And Synthesis ◽  
Vaccine Antigens

Nanocarriers with various compositions and biological properties are frequently used systems for in-vitro/in-vivo vaccination and gene transfer. In recent years, developments in nanotechnology have focused on the design and synthesis of nanocarriers that have new properties and can be modified for gene and vaccine delivery. In the favorable results obtained from in-vivo studies performed, they increase interest in these developments and pave the way for their therapeutic use. Nanocarriers have become increasingly important because they can stabilize vaccine antigens and serve as adjuvants, with the advantage of easily transporting genetic material to the target site. In nanocarriers, the molecules involved are adsorbed to the surface or encapsulated in particulates. At the same time, surface modification of nanoparticles allows these systems to carry cargo molecules easily to target site. Among the most studied nanocarriers, lipidic and polymeric systems dendrimers, inorganic nanoparticles, cyclodextrins, cell penetration peptides, and ISCOMs are attracting attention.

scholarly journals Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6559
Author(s):  
Ahmed A. Al-Karmalawy ◽  
Mai M. Farid ◽  
Ahmed Mostafa ◽  
Alia Y. Ragheb ◽  
Sara H. Mahmoud ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Antiviral Drug ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites ◽  
Flavonoid Aglycones

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

1,3,5-Pyrazoline Derivatives in CNS Disorders: Synthesis, Biological Evaluation and Structural Insights through Molecular Docking

2020 ◽  
Vol 19 (6) ◽  
pp. 448-465
Author(s):  
Himanshi Sharma ◽  
Pooja A. Chawla ◽  
Rohit Bhatia
Keyword(s):  
In Silico ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hydroxyl Group ◽  
Spectral Techniques ◽  
Lipinski’S Rule

Background: Anxiety and oxidative stress are the common disorders prevailing in the modern age. Many new pyrazoline derivatives have been synthesized and patented, but there is still continuous research in progress to explore antidepressant and antioxidant potential of pyrazoline scaffold. Objective: The present work was carried out to synthesize, characterize and evaluate the pharmacological potential of 1,3,5-Pyrazoline derivatives. Methods: Ten new 1,3,5-Pyrazoline derivatives were synthesized and characterized by IR, 1HNMR and mass spectral techniques. The synthesized pyrazoline derivatives were investigated for their in vivo antidepressant activity by Tail Suspension Test (TST) and in vitro antioxidant activity by FRAP and DPPH assay methods. The docking studies and in silico ADME and toxicity characteristics were also evaluated. Results: Among the synthesized analogues, IVh showed the highest antidepressant activity with a significant reduction in the duration of immobility. The compound IVh emerged as the most potent antioxidant compound due to the presence of an electron releasing hydroxyl group. Docking studies of most potent compounds revealed good interaction points with the MAO-A enzyme. The compounds were found to obey Lipinski’s Rule of Five and displayed the least in silico toxicity profile. Conclusion: The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.

Design and synthesis of specific colivelin derivatives for in vitro and in vivo studies

2011 ◽  
Author(s):  
Myrta Kostomoiri ◽  
Christos Zikos ◽  
Dimitra Benaki ◽  
Jiřina Slaninová ◽  
Ioannis Pirmettis ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Design And Synthesis

scholarly journals 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Humberto de Carvalho Aragão Neto ◽  
Diogo Vilar da Fonsêca ◽  
Renan Marinho Braga ◽  
Marcus Tullius Scotti ◽  
Terezinha Weyne Araújo Borges do Nascimento ◽  
...  
Keyword(s):  
In Silico ◽  
Antinociceptive Effect ◽  
Site Investigation ◽  
Docking Studies ◽  
A2a Receptors ◽  
Proinflammatory Mediators ◽  
Reduction Activity ◽  
Anti Inflammatory

2-Allylphenol (2-AP) is a synthetic phenylpropanoid, structurally related to cardanol, thymol, and ortho-eugenol. Phenylpropanoids are described in the literature as being capable of promoting biological activity. Due to the similarity between 2-AP and other bioactive phenylpropanoids, the present research aims at evaluating the antioxidant, antinociceptive, and anti-inflammatory potential of 2-AP in silico, in vitro, and in vivo. At 30 min prior to the start of in vivo pharmacological testing, administration of 2-AP (25, 50, 75, and 100 mg/kg i.p.), morphine (6 mg/kg i.p.), dexamethasone (2 mg/kg s.c.), or vehicle alone was performed. In the acetic acid-induced abdominal writhing tests, pretreatment with 2-AP significantly reduced the number of abdominal writhes, as well as decreased licking times in the glutamate and formalin tests. Investigation of the mechanism of action using the formalin model led to the conclusion that the opioid system does not participate in its activity. However, the adenosinergic system is involved. In the peritonitis tests, 2-AP inhibited leukocyte migration and reduced releases of proinflammatory mediators TNF-α and IL-1β. In vitro antioxidant assays demonstrated that 2-AP presents significant ability to sequester superoxide radicals. In silico docking studies confirmed interaction between 2-AP and the adenosine A2a receptor through hydrogen bonds with the critical asparagine 253 residues present in the active site. Investigation of 2-AP demonstrated its nociception inhibition and ability to reduce reactive oxygen species. Its interaction with A2a receptors may well be related to proinflammatory cytokines TNF-α and IL-1β reduction activity, corroborating its antinociceptive effect.

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