scholarly journals Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies

2018 ◽  
Vol 21 (1s) ◽  
pp. 1
Author(s):  
Samaa Alrushaid ◽  
Neal M. Davies ◽  
Judy E. Anderson ◽  
Tyson Le ◽  
Jaime A. Yáñez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Antioxidant Activity ◽  
In Silico ◽  
Dose Assessment ◽  
Metabolic Enzyme ◽  
Skin Permeability ◽  
Potential Candidate ◽  
Human Cardiomyocytes

PURPOSE: MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. METHODS: In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. RESULTS: MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 μM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels.CONCLUSIONS: The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or β-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies

2016 ◽  
Vol 13 (3) ◽  
pp. 206-219 ◽  
Author(s):  
Felicia Carotenuto ◽  
Alessandra Costa ◽  
Maria Cristina Albertini ◽  
Marco Bruno Luigi Rocchi ◽  
Alexander Rudov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
In Silico ◽  
Skeletal Muscle Regeneration ◽  
In Silico Studies

Potential Papain-like Protease Inhibitors against COVID-19: A Comprehensive In Silico Based Review

2021 ◽  
Vol 25 ◽  
Author(s):  
Neetu Agrawal ◽  
Shilpi Pathak ◽  
Ahsas Goyal
Keyword(s):  
In Silico ◽  
Chemical Compounds ◽  
Potential Candidate ◽  
In Vivo Experiments ◽  
Drug Databases ◽  
In Silico Studies ◽  
Approved Drugs ◽  
Fda Approved Drugs

: The entire world has been in a battle against the COVID-19 pandemic since its first appearance in December 2019. Thus researchers are desperately working to find an effective and safe therapeutic agent for its treatment. The multifunctional coronavirus enzyme papain-like protease (PLpro) is a potential target for drug discovery to combat the ongoing pandemic responsible for cleavage of the polypeptide, deISGylation, and suppression of host immune response. The present review collates the in silico studies performed on various FDA-approved drugs, chemical compounds, and phytochemicals from various drug databases and represents the compounds possessing the potential to inhibit PLpro. Thus this review can provide quick access to a potential candidate to medicinal chemists to perform in vitro and in vivo experiments who are thriving to find the effective agents for the treatment of COVID-19.

scholarly journals The synthesis and the antioxidant activity of 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2a,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 251-258
Author(s):  
Sergii Demchenko ◽  
Hanna Yeromina ◽  
Yulia Fedchenkova ◽  
Zinaida Ieromina ◽  
Vitaliy Yaremenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Carboxylic Acid ◽  
In Silico ◽  
Pharmacokinetic Profile ◽  
High Antioxidant Activity ◽  
Pharmacological Screening

New 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives have been designed, synthesized and evaluated for their in vitro antioxidant activity under conditions of the artificial oxidative stress using ionol, ascorbic acid and α-tocopherol as the reference drugs. It has been found that 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carbothionic acid derivatives 9b, 9c, 9d, 9e, 9f, 9i and 1-phenoxymethyl-4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8-triazacyclopenta[cd]azulene-3-carboxylic acid phenylamide 10 reveal a high antioxidant activity and a good in silico pharmacokinetic profile. The data obtained allowed us to select the most promising objects from the substances synthesized for further pharmacological screening for the presence of the antioxidant activity in vivo.

scholarly journals A novel in silico tool for dose assessment in cell culture nanotoxicology

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Ermes Botte ◽  
Pietro Vagaggini ◽  
Joana Costa ◽  
Lara Faccani ◽  
Ilaria Zanoni ◽  
...  
Keyword(s):  
Cell Culture ◽  
Dose Response ◽  
In Silico ◽  
Computational Approach ◽  
Engineered Nanomaterials ◽  
Dose Assessment ◽  
Biological Dose ◽  
Toxicity In Vitro

Dose assessment is essential for understanding the mechanisms triggering nanomaterial toxicity in vitro and for meaningful translations to in vivo. We propose a novel computational approach for improving the accuracy of biological dose-response characterization, demonstrating its robustness for insoluble Engineered Nanomaterials (ENMs).

scholarly journals Antioxidant Activity and Toxic Effects of Phosphorus-Containing Derivatives of 2,6-Di-tert-Butylphenol in silico and in vitro, in vivo

2019 ◽  
Vol 75 (1) ◽  
Author(s):  
Maria Aleksandrovna Polovinkina ◽  
Victoria Pavlovna Osipova ◽  
Margarita Nikolaevna Kolyada ◽  
Anastasia Dmitrievna Osipova ◽  
Nadezhda Titovna Berberova ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Toxic Effects ◽  
Phosphorus Containing ◽  
Derivatives Of

scholarly journals IN VITRO ANTIOXIDANT, ANTIMICROBIAL AND ADMET STUDY OF NOVEL FURAN/BENZOFURAN C-2 COUPLED QUINOLINE HYBRIDS

2017 ◽  
Vol 9 (10) ◽  
pp. 144
Author(s):  
Anantacharya Rajpurohit ◽  
Nayak D. Satyanarayan ◽  
Sameer Patil ◽  
Kittappa M. Mahadevan ◽  
Adarsha H. J.
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Radical Scavenging ◽  
Mean Value ◽  
Pharmacokinetic Parameters ◽  
Klebsiella Pneumonia ◽  
Potential Candidate ◽  
Good Activity

Objectives: Synthesis of novel 2-(benzofuran-2-yl) and 2-(furan-2-yl) quinoline-4- carboxylates and their [2-(1-benzofuran-2-yl) quinolin-4-yl] methanol, [2-(1-furan-2-yl) quinolin-4-yl] methanol and its derivatives for antioxidant, antimicrobial and ADMET study.Methods: Synthesis was carried with conventional method and the structures were confirmed by IR, 1H NMR, 13C NMR and mass spectral analysis. The antioxidant activity was performed by DPPH and H2O2 radical scavenging method. Antimicrobial investigation was established by cup plate and food poison technique. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study of the drug was carried out in ACD/lab-2.Results: The antioxidant activity results revealed that, compounds 4b-c, 5a-b, 10c and 10f exhibited good DPPH radical and hydrogen peroxide scavenging activity. The antibacterial results revealed that, compounds 4c, 5a-b, 10b, 10d and 10f exhibited good activity against Escherichia coli, Klebsiella pneumonia and Salmonella typhimurium. Further, the antifungal activity results showed that, compounds 4c, 5c and 10c-e were showing good activity against Aspergillus flavus and Candida neoformans.  The mean value of P<0.05 were considered to be statistically significant. The ADMET results revealed that compounds emerged as a potential candidate for antioxidant and antimicrobial agents.Conclusion: The study reveals that compounds containing furan/benzofuran coupled heterocycles are play the important role for activity as they possess potent antioxidant and antimicrobial agents. The in silico ADME analysis also suggesting the compounds were in acceptable range to obey the pharmacokinetic parameters. 

Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli
Keyword(s):  
Antioxidant Activity ◽  
Biological Effects ◽  
Reducing Power ◽  
Hematological Toxicity ◽  
Protective Effects ◽  
Ferrous Ions ◽  
Polyphenolic Extract ◽  
Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

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

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.

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.

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