A new series of 2,4-thiazolidinediones endowed with potent aldose reductase inhibitory activity

Abstract In an effort to identify potent aldose reductase (AR) inhibitors, 5-(arylidene)thiazolidine-2,4-diones (1–8), which were prepared by the solvent-free reaction of 2,4-thiazolidinedione with aromatic aldehydes in the presence of urea, were examined for their in vitro AR inhibitory activities and cytotoxicity. 5-(2-Hydroxy-3-methylbenzylidene)thiazolidine-2,4-dione (3) was the most potent AR inhibitor in this series, exerting uncompetitive inhibition with a K i value of 0.445 ± 0.013 µM. The IC50 value of compound 3 for L929 mouse fibroblast cells was determined as 8.9 ± 0.66 µM, pointing out its safety as an AR inhibitor. Molecular docking studies suggested that compound 3 exhibited good affinity to the binding site of AR (PDB ID: 4JIR). Based upon in silico absorption, distribution, metabolism, and excretion data, the compound is predicted to have favorable pharmacokinetic features. Taking into account the in silico and in vitro data, compound 3 stands out as a potential orally bioavailable AR inhibitor for the management of diabetic complications as well as nondiabetic diseases.

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Blends of Thermoplastic Polyurethane and Polydimethylsiloxane Rubber: Assessment of Biocompatibility and Suture Holding Strength of Membranes

International Journal of Biomaterials ◽

10.1155/2013/240631 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Krishna Prasad Rajan ◽

Ahmed Al-Ghamdi ◽

Ramesh Parameswar ◽

G. B. Nando

Keyword(s):

Cell Proliferation ◽

Thermoplastic Polyurethane ◽

Mouse Fibroblast ◽

Tissue Cell ◽

Connective Tissue Cell ◽

L929 Mouse Fibroblast ◽

Subcutaneous Connective Tissue ◽

L929 Mouse ◽

Reactive Compatibilizer

In the present investigation, a compatibilized blend of thermoplastic polyurethane (TPU) and polydimethylsiloxane (PDMS) is prepared by using copolymer of ethylene and methyl acrylate (EMA) as a reactive compatibilizer. Detailedin vitrobiocompatibility studies were carried out for this compatibilized blend and the material was found noncytotoxic towards L929 mouse fibroblast subcutaneous connective tissue cell line. Microporosity was created on the surface of membranes prepared from the blend material by adopting the crazing mechanism. Cell proliferation and growth studies on the membranes surface showed that the microporous surface favoured ingrowth of the cells compared with a nonmicroporous surface. Suture holding strength studies indicate that the microporous membranes have enough strength to withstand the cutting and tearing forces through the suture hole. This blend material could be evaluated further to find its suitability in various implant applications.

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In vitro investigation of the cytotoxic, apoptotic and genotoxic effects of pulp capping materials on L929 mouse fibroblast cells

Journal of Research in Pharmacy ◽

10.29228/jrp.53 ◽

2021 ◽

Vol 25(5) (25(5)) ◽

pp. 608-617

Author(s):

Rosa Mhlanga CHINHEYA ◽

Murat YILMAZ ◽

Aylin ÜSTÜNDAĞ ◽

Seda İPEK ◽

Yalçın DUYDU ◽

...

Keyword(s):

Mouse Fibroblast ◽

Fibroblast Cells ◽

Genotoxic Effects ◽

Pulp Capping ◽

L929 Mouse Fibroblast ◽

In Vitro Investigation ◽

L929 Mouse

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In vitro and in silico studies on AChE inhibitory effects of a series of donepezil-like arylidene indanones

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0356 ◽

2020 ◽

Vol 45 (4) ◽

pp. 359-363

Author(s):

Belgin Sever ◽

Mehlika Dilek Altıntop ◽

Halide Edip Temel

Keyword(s):

Molecular Docking ◽

In Silico ◽

Binding Mode ◽

Docking Studies ◽

Ache Inhibitor ◽

Ache Inhibition ◽

Lipinski’S Rule ◽

In Silico Studies ◽

Orally Bioavailable

AbstractObjectiveDonepezil is the most potent acetylcholinesterase (AChE) inhibitor currently available on the market for the management of Alzheimer’s disease. In this study, it was aimed to identify potent donepezil analogues.Materials and methodsThe effects of arylidene indanones (1–10) on AChE inhibition were examined using modified Ellman’s assay. Compound 4, the most potent arylidene indanone in this series, was subjected to molecular docking to anticipate its binding mode in the AChE site (PDB code: 4EY7). The pharmacokinetic profiles of all derivatives were also predicted.ResultsCompound 4 was found as the most potent AChE inhibitor with an IC50 value of 5.93 ± 0.29 μg/mL. According to molecular docking studies, compound 4 presented favorable interactions such as π–π interactions with Trp286 and Tyr337. In silico studies revealed that the compound did not violate Lipinski’s rule of five and Jorgensen’s rule of three, making it a potential orally bioavailable agent.ConclusionCompound 4 is a feasible candidate for further experiments related to AChE inhibition.

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Synthesis, Characterization, In-Silico Docking Study and In-Vitro AntiInflammatory Activities of Novel Chalcone Derivatives

10.47363/jbbr/2021(3)133 ◽

2021 ◽

Vol 3 (2) ◽

pp. 1-6

Author(s):

R Bharathi ◽

◽

N Santhi ◽

Keyword(s):

In Silico ◽

Aromatic Aldehydes ◽

Docking Study ◽

Docking Studies ◽

In Silico Docking ◽

Therapeutic Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Important Activity

A series of chalcones were synthesised by condensation of appropriate acetophenones with appropriate aromatic aldehydes, and their anti-inflammatory activities were investigated. In comparison to standard drugs, some have been found to have important activity. In silico docking, tests on chalcones were shown to be more selective to COX-2. Further anti-inflammatory results were supported by docking studies with COX-2. The results from the anti-inflammatory and docking indicate that the synthesised compounds 3b, 3g and 3h can be seen as therapeutic drugs.

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

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180220125406 ◽

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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Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190121105851 ◽

2019 ◽

Vol 18 (31) ◽

pp. 2731-2740 ◽

Cited By ~ 3

Author(s):

Sandeep Tiwari ◽

Debmalya Barh ◽

M. Imchen ◽

Eswar Rao ◽

Ranjith K. Kumavath ◽

...

Keyword(s):

Broad Spectrum ◽

In Silico ◽

Pathogenic Bacteria ◽

In Vitro Study ◽

Docking Studies ◽

Acetate Kinase ◽

E Coli ◽

Pathogenic Escherichia Coli ◽

Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

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Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

Current Bioactive Compounds ◽

10.2174/1573407213666170828165512 ◽

2019 ◽

Vol 15 (2) ◽

pp. 257-267 ◽

Cited By ~ 3

Author(s):

Paritosh Shukla ◽

Ashok Sharma ◽

Leena Fageria ◽

Rajdeep Chowdhury

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

In Silico ◽

Antimicrobial Agents ◽

Docking Studies ◽

Bioactive Molecules ◽

Microwave Assisted Synthesis ◽

Binding Affinities ◽

In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

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A nano chitosan membrane barrier prepared via Nanospider technology with non-toxic solvent for peritoneal adhesions’ prevention

Journal of Biomaterials Applications ◽

10.1177/08853282211008109 ◽

2021 ◽

pp. 088532822110081

Author(s):

Shuo Zhang ◽

Zhuoyue Xu ◽

Xuejun Wen ◽

Changzheng Wei

Keyword(s):

Mouse Fibroblast ◽

Electrospun Membrane ◽

Adhesion Barrier ◽

Peritoneal Adhesions ◽

Elongation At Break ◽

In Vivo Experiments ◽

L929 Mouse Fibroblast ◽

Membrane Barrier ◽

L929 Mouse

Peritoneal adhesion is one of the most common postsurgical complications and can cause bowel obstruction, pelvic pain, and infertility. Setting up a physical barrier directly between the injured site and surrounding tissues is an effective solution for preventing this adverse situation. This study investigated a chitosan electrospun membrane (CSEM) as a potent anti-adhesion barrier, which was prepared by a needleless technology called Nanospider. Scanning electron microscopy revealed that CSEM is a laminated nanofiber with good mechanical properties. The fiber is uniform with the diameter distributing in the range of 100–120 nm. The tensile strength can reach 27.45 ± 6.30 MPa with a maximum elongation at break of 18.50 ± 1.44%, which makes it stick easily to damaged parts but not to be easily damaged by tissue friction. The growth of S. aureus on CSEM was 59.18% lower than the control at 10 h, which indicates its better antibacterial property. In addition, CSEM has good coagulant and biocompatibility characteristics. It can perform hemostatic function within 10 min and the L929 mouse fibroblast viability on it was 92.18% ± 1.08% on the seventh day. In vivo experiments indicated that CSEM significantly prevented peritoneal adhesions within four weeks after surgery with wound surface coverage. These results indicate that CSEM is a promising anti-adhesion barrier material.

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In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽

10.1186/s13099-021-00443-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Padikkamannil Abishad ◽

Pollumahanti Niveditha ◽

Varsha Unni ◽

Jess Vergis ◽

Nitin Vasantrao Kurkure ◽

...

Keyword(s):

Escherichia Coli ◽

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Antimicrobial Efficacy ◽

Drug Resistant ◽

Protein Motifs ◽

Phytochemical Compounds ◽

In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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