scholarly journals 2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis, biological evaluation, molecular docking, and pharmacokinetic studies

2021 ◽  
pp. 103449
Author(s):  
Adnan Cetin ◽  
Ercan Bursal ◽  
Fikret Türkan
Keyword(s):  
Molecular Docking ◽  
Biological Evaluation ◽  
Pharmacokinetic Studies ◽  
Glutathione S Transferase

scholarly journals Ameliorative Role of Nutraceutical Quercetin and its Derivatives Against Cognitive Impairment Process Induced by Lead Exposure in Drosophila melanogaster(Fruit Fly)

2021 ◽  
Vol 30 (2) ◽  
pp. 135-142
Author(s):  
Abubakar lema Abdullahi ◽  
A. A. Lema ◽  
K. Jibrin ◽  
W. Nuraddeen ◽  
E. M. Alexander
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Docking ◽  
Therapeutic Index ◽  
Fruit Fly ◽  
Acetylcholinesterase Activity ◽  
Docking Studies ◽  
Pharmacokinetic Studies ◽  
Glutathione S Transferase ◽  
High Therapeutic Index ◽  
In Silico Toxicity

Cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition through the free radical generation and epigenetic effects. Several pieces of literature have identified a correlation between exposure to lead and neurodegenerative disorders. Harwich strain Drosophila melanogaster was exposed to lead acetate for two weeks, and changes in pulse transmission by acetylcholinesterase and systemic redox were evaluated. Besides, molecular docking studies of acetylcholinesterase against Quercetin and its most common derivatives contained in food have been performed. Pharmacokinetic studies on Quercetin and its derivatives have also been performed in silico toxicity. The data obtained showed alterations in antioxidant enzymes and molecules such as catalase, glutathione-S-transferase, and glutathione. Upregulation of acetylcholinesterase activity was observed after treatment with Quercetin. In molecular docking tests, Quercetin and its derivatives were found to bind to acetylcholinesterase's active and peripheral pockets. Pharmacokinetic studies demonstrate moderate solubility, high therapeutic index, excellent absorption potential, hepatoprotective and non-mutagenic properties. With other antioxidant molecules, Quercetin may also play a crucial role in avoiding the development of Alzheimer's and associated antioxidant disorders.  

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 591
Author(s):  
Toshihiko Matsuo ◽  
Shihui Liu ◽  
Tetsuya Uchida ◽  
Satomi Onoue ◽  
Shinsaku Nakagawa ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Pharmacokinetic Studies ◽  
Retinal Neurons ◽  
Retinal Cells ◽  
Intravitreous Injection ◽  
Rcs Rats ◽  
Photoelectric Dye ◽  
Dark Conditions

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

scholarly journals Synthesis and Biological Evaluation of a Novel Glycidyl Metharcylate/Phaytic Acid-Based on Bagasse Xylan Composite Derivative

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2084
Author(s):  
Mingkun Li ◽  
Heping Li ◽  
Hongli Liu ◽  
Zhiming Zou ◽  
Chaoyu Xie
Keyword(s):  
Lung Cancer ◽  
Thermal Stability ◽  
Ionic Liquid ◽  
Molecular Docking ◽  
Phytic Acid ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Potential Candidate ◽  
Reaction Conditions ◽  
Cell Proliferation Inhibition

The development of natural biomass materials with excellent properties is an attractive way to improve the application range of natural polysaccharides. Bagasse Xylan (BX) is a natural polysaccharide with various biological activities, such as antitumor, antioxidant, etc. Its physic-chemical and biological properties can be improved by functionalization. For this purpose, a novel glycidyl metharcylate/phytic acid based on a BX composite derivative was synthesized by a free radical polymerization technique with glycidyl metharcylate (GMA; GMABX) and further esterification with phytic acid (PA; GMABX-PA) in ionic liquid. The effects of the reaction conditions (i.e., temperature, time, initiator concentration, catalyst concentration, GMA concentration, PA concentration, mass of ionic liquid) on grafting rate(G), conversion rate(C) and degree of substitution(DS) are discussed. The structure of the composite material structure was confirmed by FTIR, 1H NMR and XRD. SEM confirmed the particle morphology of the composite derivative. The thermal stability of GMABX-PA was determined by TG-DTG. Molecular docking was further performed to study the combination mode of the GMABX-PA into the active site of two lung cancer proteins (5XNV, 2EB2) and a blood cancer protein (2M6N). In addition, tumor cell proliferation inhibition assays for BX, GMABX-PA were carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetraz -olium bromide (MTT) method. The results showed that various reaction conditions exhibited favorable gradient curves, and that a maximum G of 56% for the graft copolymerization and a maximum DS of 0.267 can be achieved. The thermal stability was significantly improved, as demonstrated by the fact that there was still 60% residual at 800 °C. The molecular docking software generated satisfactory results with regard to the evaluated binding energy and combining sites. The inhibition ratio of GMABX-PA on NCI-H460 (lung cancer cells) reached 29.68% ± 4.45%, which is five times higher than that of BX. Therefore, the material was shown to be a potential candidate for biomedical applications as well as for use as a heat resistant material.

scholarly journals Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

2016 ◽  
Vol 64 (9) ◽  
pp. 1281-1287 ◽  
Author(s):  
Sulunay Parlar ◽  
Gulsah Bayraktar ◽  
Ayse Hande Tarikogullari ◽  
Vildan Alptüzün ◽  
Ercin Erciyas
Keyword(s):  
Molecular Docking ◽  
Cholinesterase Inhibitors ◽  
Docking Study ◽  
Biological Evaluation ◽  
Pyridinium Salts ◽  
Molecular Docking Study
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