In silico Assessment and Molecular Docking Studies of Some Phyto-Triterpenoid for Potential Disruption of Mortalin-p53 Interaction

Human hepatocellular carcinoma (HCC), the most common type of liver cancer, represents the second most common cause of death from cancer worldwide. The high toxicity and side effects of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. Mortalin/mtHsp70, a stress response protein, has been reported to contribute to the process of carcinogenesis in several ways, including the inhibition of the transcriptional activation of p53. This study conducted a molecular docking study of 41 phyto triterpenes originated from Vietnamese plants for potential Mortalin inhibition activity. Nine compounds were considered as promising inhibitors based on the analysis of binding affinity and drug-like and pharmacokinetic properties.

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Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

Current Organic Synthesis ◽

10.2174/1570179417666200407130122 ◽

2020 ◽

Vol 17 (5) ◽

pp. 367-381

Author(s):

Pintu Pathare ◽

Sunil Tekale ◽

Rafique Shaikh ◽

Manoj Damale ◽

Jaiprakash Sangshetti ◽

...

Keyword(s):

Molecular Docking ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Docking Study ◽

Docking Studies ◽

Pharmacokinetic Parameters ◽

Molecular Docking Study ◽

Antimicrobial Drugs ◽

Discovery Studio ◽

Pharmacokinetic Properties

Background: The search for new antimicrobial drugs is a never ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to human kind. Objective: The present studies were aimed to synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones. Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against diffenet bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict toxicity profile of the compounds using FAFDrugs2 predictor. Results: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives. Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

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In Vitro Antioxidant, Antimicrobial and Molecular Docking Studies of Fosphenytoin and Regadenoson Impurities

Science & Technology Journal ◽

10.22232/stj.2020.08.01.08 ◽

2020 ◽

Vol 8 (1) ◽

pp. 63-69

Author(s):

S. Sathiyanarayanan ◽

◽

C.S. Venkatesan ◽

S. Kabilan ◽

◽

...

Keyword(s):

Molecular Docking ◽

Drug Product ◽

Active Pharmaceutical Ingredient ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Gaba A ◽

Pharmacokinetic Properties ◽

Approved Drugs

Regadenoson and Fosphenytoin are USFDA approved drugs which is used for coronary vasodilator and convulsive status epileptics respectively. It is quite natural that low levels of reagents or side products are present in the final active pharmaceutical ingredient (API) or drug product as impurities. Such impurities may have unwanted toxicities, including genotoxicity and carcinogenicity. Hence, it is important to study on impurities present in both the drugs. There are 9 impurities were identified from both drugs and studied pharmacokinetic properties using Qikprop module from Schrödinger software. From the 9 compounds of both the drug’s impurities, 5 compounds obey the Lipinski rule of five and the remaining compounds are having 1 to 3 penalties. All the compounds were subjected to molecular docking study with thermo stabilised HUMAN A2A Receptor with adenosine bound protein (PDB ID: 2YDO) for regadenoson impurities and fosphenytoin impurities were docked with Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation A protein (PDB id: 6D6U). All the compounds are showed very good interaction with docked proteins. Further selected compound subjected to in vitro Antibacterial (Gram positive, Gram negative), Antifungal and Antioxidant (DPPH and FRAP) studies.

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Synthesis and molecular docking studies of some novel Schiff bases incorporating 6-butylquinolinedione moiety as potential topoisomerase IIβ inhibitors

Royal Society Open Science ◽

10.1098/rsos.172407 ◽

2018 ◽

Vol 5 (6) ◽

pp. 172407 ◽

Cited By ~ 3

Author(s):

Hany M. Hassanin ◽

Rabah A. T. Serya ◽

Wafaa R. Abd Elmoneam ◽

Mai A. Mostafa

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Docking Study ◽

Docking Studies ◽

Complex Compounds ◽

Inhibition Activity ◽

Molecular Docking Study ◽

Dna Topoisomerase ◽

Mcf 7

A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the D iscovery S tudio 2.5 software, where they showed very interesting ability to intercalate the DNA–topoisomerase complex. Compounds 2a , 2c and 2f showed high docking score values (82.36% −29.98 kcal mol −1 for compound 2a , 78.18% −26.98 kcal mol −1 for compound 2c and 78.65, −28.11 kcal mol −1 for compound 2f ) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.

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Anti-Cancer, Anti-Osteoporosis, and Molecular Docking Studies of Novel Chalcone and Epoxy Chalcone

Biointerface Research in Applied Chemistry ◽

10.33263/briac125.66686685 ◽

2021 ◽

Vol 12 (5) ◽

pp. 6668-6685

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Cell Cycle Arrest ◽

Docking Study ◽

Docking Studies ◽

Stable Complex ◽

Molecular Docking Study ◽

Cycle Arrest ◽

Anti Cancer ◽

Induced Apoptosis

Cancer is a leading cause of death worldwide. Osteoporosis is a bone condition that causes the bones to become porous and lose density. Discovering, searching, and develop for a drug against cancer and at the same time preventing osteoporosis is very important. Chalcone and epoxy have an interest as potential drug candidates due to their easy synthesis. The present study target compounds were screened for potential anti-cancer against different cell lines (HepG2, MDA-MB-231, A375, A549, MCF-7, and HCT116) and anti-osteoporosis against cell line (MC3T3-E1). A new series of compounds evaluation by MTT assay to determine the IC50, and study apoptosis and docking study. The most potent activities were the effects of the compounds CH2, CH3, and CH4 on the MDA-MB-231 cells and those of the compounds CH7 and CH9 on the HepG2. The CH7 compound proved non-cytotoxic but was antiproliferative and caused cell cycle arrest at the G0/G1 and G2/M phases. Also, the CH7, CH9, and E1 compounds displayed excellent anti-osteoporosis activity. The docking analysis showed good binding energy. The compounds CH2, CH3, and CH4 exhibited activity towards MDA-MB-231 cells and CH7 against HepG2, with induced apoptosis and cell cycle arrest, others compounds showed no significant cytotoxic activity. While compounds CH7, CH8, CH9, and E1 showed good toxicity against MC3T3-E1. The molecular docking study revealed that there was evidence of good interactions and the most stable complex for inhibition.

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Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

Pharmaceuticals ◽

10.3390/ph14070685 ◽

2021 ◽

Vol 14 (7) ◽

pp. 685

Author(s):

Sandra Amanda Kozieł ◽

Monika Katarzyna Lesiów ◽

Daria Wojtala ◽

Edyta Dyguda-Kazimierowicz ◽

Dariusz Bieńko ◽

...

Keyword(s):

Molecular Docking ◽

Serum Proteins ◽

Docking Study ◽

Minor Groove ◽

Docking Studies ◽

Minor Groove Binding ◽

Binding Modes ◽

Groove Binding ◽

Molecular Docking Study ◽

Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

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Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

Physical Sciences Reviews ◽

10.1515/psr-2019-0136 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Joshua Oluwasegun Bamidele ◽

George Oche Ambrose ◽

Oluwaseun Suleiman Alakanse

Keyword(s):

Molecular Docking ◽

Liver Toxicity ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Docking Analysis ◽

Computational Docking ◽

Drug Candidates ◽

Expression Rate ◽

Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

Plants ◽

10.3390/plants11020208 ◽

2022 ◽

Vol 11 (2) ◽

pp. 208

Author(s):

Ahlam Elwekeel ◽

Dalia El Amir ◽

Enas I. A. Mohamed ◽

Elham Amin ◽

Marwa H. A. Hassan ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Docking Studies ◽

Antidiabetic Activity ◽

Flavonoid Glycosides ◽

Total Phenolic ◽

Cytotoxic Activities ◽

Alcoholic Extract ◽

Molecular Docking Study

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

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Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22634 ◽

2020 ◽

Vol 32 (6) ◽

pp. 1482-1490

Author(s):

Manju Mathew ◽

Raja Chinnamanayakar ◽

Ezhilarasi Muthuvel Ramanathan

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Study ◽

Docking Studies ◽

Moderate Activity ◽

Molecular Docking Study ◽

Adme Prediction ◽

Antimicrobial Studies ◽

In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

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Anti-Cancer and Anti-Inflammatory Potential of the Green Synthesized Silver Nanoparticles of the Red Sea Sponge Phyllospongia lamellosa Supported by Metabolomics Analysis and Docking Study

Antibiotics ◽

10.3390/antibiotics10101155 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1155

Author(s):

Areej A. Al-Khalaf ◽

Hossam M. Hassan ◽

Aisha M Alrajhi ◽

Rania Ali El Hadi Mohamed ◽

Wael N. Hozzein

Keyword(s):

Silver Nanoparticles ◽

Molecular Docking ◽

Red Sea ◽

Docking Study ◽

Chloroform Extract ◽

Docking Studies ◽

Silver Nanostructure ◽

Anti Cancer ◽

Anti Inflammatory ◽

Metabolomics Analysis

Background: The Red Sea sponges have been endorsed as a plentiful source of bioactive compounds with promising anti-cancer and anti-inflammatory activities; therefore, exploring their potential as a source of anti-cancer metabolites has stimulated a growing research interest. Purpose: To investigate the anti-cancer and anti-inflammatory potential of the Red Sea sponges, in their bulk and silver nanostructure. Metabolomics analysis of the selected sponge followed by molecular docking studies, will be conducted to explore and predict the secondary metabolites that might provide its capability of inhibiting cancer. Materials and Methods: We prepared a chloroform extract (CE) and ethyl acetate extract (EE) of the Red Sea sponge Phyllospongia lamellosa synthesized silver nanoparticles. The prepared silver nanoparticles were characterized through UV–vis spectrophotometric, transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR) analyses. Testing for their anti-cancer activities was performed against MCF-7, MDB-231, and MCF-10A cells. Anti-inflammatory activity against COX-1 and 2 was assessed. Furthermore, liquid chromatography–mass spectrometry (LC–MS)-based metabolomics analysis and molecular docking were also applied.

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