Molecular Docking Study of Active Diazenyl Scaffolds as Inhibitors of Essential Targets Towards Antimicrobial Drug Discovery

2019 ◽  
Vol 20 (15) ◽  
pp. 1587-1602 ◽  
Author(s):  
Harmeet Kaur ◽  
Sudhir Gahlawat ◽  
Jasbir Singh ◽  
Balasubramanian Narasimhan
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Schiff Bases ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Antifungal Drugs ◽  
Molecular Docking Study ◽  
Dna Topoisomerase ◽  
Standard Drug

Background: The diazenyl compounds (-N=N- linkage) have been reported to have antimicrobial activity. In modern drug discovery, the drug-receptor interactions are generally explored by the molecular docking studies. Materials and Methods: Three categories of diazenyl scaffolds were screened for the docking studies to explore the binding mechanism of interaction with various microbial targets. The diazenyl Schiff bases (SBN-20, SBN-21, SBN-25, SBN-33, SBN-39, SBN-40 and SBN-42), naphthol pharmacophore based diazenyl Schiff bases (NS-2, NS-8, NS-12, NS-15, NS-21, and NS-23), morpholine based diazenyl chalcones (MD-6, MD-9, MD-14, MD-16, MD-20, and MD-21) were docked against various bacterial and fungal proteins in comparison with different standard drugs. Further, the drug likeliness and ADME properties of these molecules were predicted by QikProp module of the Schrodinger software. Results: Most of the derivatives had shown less docking scores and binding energies towards bacterial proteins, such as dihydropteroate synthase (PDB:2VEG), glucosamine-6-phosphate synthase (PDB:2VF5), dihydrofolate reductase (PDB:3SRW) in comparison with the standard drugs. The naphthol based diazenyl Schiff bases NS-21 and NS-23 were predicted to act on the cytochrome P450 sterol 14-alpha-demethylase (CYP51) (PDB:5FSA) involved in sterol biosynthesis, an essential target for antifungal drugs. The derivative MD-6, NS-2, NS-21, and NS-23 had shown high docking scores against bacterial DNA topoisomerase (PDB:3TTZ) in comparison with the standard drug ciprofloxacin. Further, most of the synthesized derivatives had shown drug like characters. Conclusion: Hence, these compounds can be developed as novel antibacterial agents as potent DNA topoisomerase inhibitors and antifungal agents as CYP51 inhibitors.

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.

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

2018 ◽  
Vol 5 (6) ◽  
pp. 172407 ◽  
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.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

scholarly journals Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2977
Author(s):  
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip ◽  
Michail Georgakis ◽  
Lucio R. Montero Valenzuela ◽  
Mohamed Hamza ◽  
Ehab Farag ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Main Protease ◽  
Binding Pockets

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

scholarly journals DFT Study, POM Analyses and Molecular Docking of Novel Oxazaphosphinanes: Identification of Antifungal Pharmacophore Site

2020 ◽  
Vol 20 (2) ◽  
pp. 440 ◽  
Author(s):  
Khadidja Otmane Rachedi ◽  
Rania Bahadi ◽  
Mohamed Aissaoui ◽  
Taibi Ben Hadda ◽  
Billel Belhani ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Docking Study ◽  
Docking Studies ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Chemical Parameters ◽  
Molecular Docking Study ◽  
Physico Chemical ◽  
Pom Analyses

A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of series of oxazaphosphinanes derivatives 1a-1f containing potential antifungal O,N-pharmacophore. Molecular docking study was performed in order to evaluate synthesized compounds their possible antifungal properties and their interactions in the binding site. Molecular docking studies revealed that the compounds 1a-1f have the potential to become lead molecules in the drug discovery process. The six compounds 1a–1f analyzed here were previously synthesized by our group.

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

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