scholarly journals Synthesis, Molecular Docking, and Evaluation of Some New Curcumin Analogs as Antimalarial Agents

2021 ◽  
Vol 21 (2) ◽  
pp. 452
Author(s):  
Endang Astuti ◽  
Tri Joko Raharjo ◽  
Putra Boang Manalu ◽  
Ilham Satria Putra ◽  
Stephanus Satria Waskitha ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Aldol Condensation ◽  
Antimalarial Activity ◽  
Docking Study ◽  
Docking Studies ◽  
Curcumin Analog ◽  
Molecular Docking Study ◽  
Antimalarial Agents ◽  
Curcumin Analogs ◽  
Ic50 Value

This research involves the synthesis, antimalarial evaluation, and molecular docking of several curcumin analogs. A total of six curcumin analog compounds were synthesized using aldol condensation using hydrochloric acid and sodium hydroxide catalysts. The synthesized compounds were elucidated using FTIR, 1H-NMR, 13C-NMR, and LC-MS/MS. Subsequently, all curcumin analogs were tested as an antimalarial agent against Plasmodium falciparum 3D7 strain, and their mechanism of action was evaluated through a molecular docking study. Six curcumin analogs, i.e. 2,6-bis(2-hydroxybenzylidene)cyclohexanone; 2,6-bis(2-hydroxybenzylidene)cyclopentanone; 1.5-bis(2-hydroxyphenyl)penta-1,4-diene-3-one; 2,6-bis(3-hydroxybenzylidene)cyclo-hexanone; 2,6-bis(3-hydroxybenzylidene)cyclopentanone; and 1,5-bis(3-hydroxy-phenyl)penta-1,4-diene-3-one have been successfully synthesized. In addition, 2,6-bis(2-hydroxybenzylidene) cyclopentanone demonstrated the lowest IC50 value and binding affinity of 0.04 µM and -7.6 kcal/mol, respectively. Based on molecular docking studies, this compound also showed the most potent antimalarial activity targeted at PfATP6.

scholarly journals Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1002 ◽  
Author(s):  
Noor Almandil ◽  
Muhammad Taha ◽  
Rai Farooq ◽  
Amani Alhibshi ◽  
Mohamed Ibrahim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Thymidine Phosphorylase ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Substitution Pattern ◽  
Structure Activity ◽  
Ic50 Value ◽  
Quinoxaline Derivatives ◽  
Better Than

We have synthesized quinoxaline analogs (1–25), characterized by 1H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

Design, Synthesis, Molecular Docking Study and Anti-Hepatocellular Carcinoma Evaluation of New Bis-Triazolothiadiazines

2020 ◽  
Vol 20 (9) ◽  
pp. 788-800 ◽  
Author(s):  
Sobhi M. Gomha ◽  
Zeinab A. Muhammad ◽  
Elham Ezz El-Arab ◽  
Amira M. Elmetwally ◽  
Abdelaziz A. El-Sayed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Reference Drug ◽  
Ic50 Value

Objective: The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives. Methods: The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method. Results: Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM). Conclusion: Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

Computational and Kinetic Studies of Acetylcholine Esterase Inhibition by Phenserine

2019 ◽  
Vol 25 (18) ◽  
pp. 2108-2112 ◽  
Author(s):  
Shams Tabrez ◽  
Ghazi A. Damanhouri
Keyword(s):  
Molecular Docking ◽  
Mixed Type ◽  
Kinetic Studies ◽  
Docking Study ◽  
Docking Studies ◽  
Catalytic Site ◽  
Dependent Manner ◽  
Molecular Docking Study ◽  
Ic50 Value ◽  
Current Article

Background: The inhibition of cholinesterase enzymes is one of the promising strategies to manage several neurological disorders that include Alzheimer's disease (AD). Material and Methods: In the current article, we estimated the potential inhibition of acetyl cholinesterase (AChE) by phenserine using slightly modified Ellman assay. To find out the binding interactions of phenserine with the catalytic site of AChE, a molecular docking study was also performed. Results: Phenserine was found to inhibit Electrophorus electricus AChE in a dose-dependent manner with an IC50 value of 0.013 µM. The kinetic analyses indicate that phenserine inhibits AChE in a mixed type manner (competitive and uncompetitive) with Ki values of 0.39 μmole/l and 0.21 µmole/l, respectively. On the other hand, Km and Vmax values were found to be 0.17 µM and 0.39 µM, respectively. The molecular docking studies indicate efficient binding of phenserine through 6 hydrogen bonds, 4 pi-alkyl interactions, and 1 pi-pi interaction within the AChE catalytic pocket. Conclusion: Results of our computational and kinetics studies indicated a mixed type inhibition by phenserine at AChE catalytic site.

scholarly journals Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

2019 ◽  
Author(s):  
Noor Barak Almandil ◽  
Muhammad Taha ◽  
Rai Khalid Farooq ◽  
Amani Alhibshi ◽  
Mohamed Ibrahim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Thymidine Phosphorylase ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Substitution Pattern ◽  
Structure Activity ◽  
Ic50 Value ◽  
Quinoxaline Derivatives ◽  
Better Than

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

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

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.

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

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.

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

Plants ◽  
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.

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

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

scholarly journals Synthesis and Molecular Docking Studies of Coumarinyl Thiazole as Cell Division Protein Kinase 2 Inhibitor

2019 ◽  
Vol 31 (11) ◽  
pp. 2453-2456
Author(s):  
J. Brindha ◽  
T.F. Abbs Fen Reji
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Protein Kinase ◽  
Screening Tool ◽  
Docking Study ◽  
Docking Studies ◽  
Autodock Vina ◽  
Molecular Docking Study ◽  
Molecular Docking Studies ◽  
Cell Division Protein

A series of 2-alkylamino-4-(3-coumarinyl)thiazoles were synthesized, characterized and evaluated their anticancer activity through molecular docking studies. Cell division protein kinase 2 (PDB code: 1KE9) is selected as a target and the compounds which obeys Lipinski rule of five is selected as a ligand. Molecular docking study is carried out using AutoDock Vina in PyRx virtual screening tool. This study revealed that all the compounds are active against the molecular target and compounds 5a and 5c have the highest docking score.

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

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