Design, Synthesis, Antimicrobial Evaluation and Molecular Docking Studies of Some Novel Monoterpenoids Substituted Quinoxaline Thiosemicarbazide Derivatives

2021 ◽  
Vol 14 (2) ◽  
pp. 5424-5435
Author(s):  
Bipin Bihari ◽  
Girendra Kumar Gautam ◽  
Akash Ved
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Docking Studies ◽  
Dilution Method ◽  
Molecular Docking Studies ◽  
Fungal Strains ◽  
Antimicrobial Evaluation ◽  
Thiosemicarbazide Derivatives ◽  
Antibacterial And Antifungal

Owing to the increasingly serious problems caused by multidrug resistance in acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. The present study aims to increase the antimicrobial activity of quinoxaline thiosemicarbazide derivatives by introducing a hydrophobic alkyl chain, an electron-releasing group in the ring, and substitution by some acyclic, cyclic and bicyclic monoterpenes and their antimicrobial evaluation against various strains with molecular docking studies. The lead molecule (1E, 4E)-1-(7-chloro-3-isopropyl- quinoxalin-2(1H)-ylidene) thiosemicarbazide was synthesized and condensed with various monoterpenes to synthesize different derivatives. The structures of compounds were confirmed through IR., NMR & mass spectroscopy. The synthesized derivatives were evaluated in vitro for antibacterial  and  antifungal activities against various strains using the agar dilution method. Molecular docking studies of the derivatives (Va– Vg) were performed to find out essential binding sites against target protein (PDB: 3 FAP, receptor: FKBP 12) using Autodock 4.2. The compounds Va, Vd, Vf & Vg exhibited potent antibacterial and antifungal activity. Among all these compounds Vd was found to exhibit more potent activity against gram +Ve, gram –Ve bacterial and fungal strains at MIC 0.19 μg/ml, 0.39μg/ml, and 1.56 μg/ml respectively. The docking studies of all the compounds exhibit potent binding energy, but the compound Vd exhibit interactive binding energy (-9.98 kcal/mol) to the active pockets of the receptor FKBP12. The compound Vd interacting with various active sites of amino acids of receptors like PHE128, TRP190, TYR26, VAL55, ILE56, PHE99, and TRP59. In terms of structure- activity relationship study it is revealed that the activity profile against bacterial and fungal strains was altered by the formation of monoterpenoid substituted (1E, 4E)-1-(7- chloro-3-isopropylquinoxalin-2(1H)-ylidene) thiosemicar- bazide derivatives. The study reveals that bicyclic monoterpenes substituted compounds exhibit greater activity than cyclic and acyclic. The molecular docking studies also showed that all the compounds exhibit good docking energy to bind and inhibit the FKBP12 receptor.

Antioxidant, antimicrobial, and molecular docking studies of novel chalcones and Schiff bases bearing 1, 4-naphthoquinone moiety

2021 ◽  
Vol 19 ◽  
Author(s):  
Nadia Ali Ahmed Elkanzi ◽  
Hajer Hrichi ◽  
Rania B. Bakr
Keyword(s):  
Molecular Docking ◽  
Schiff Bases ◽  
Active Sites ◽  
Radical Scavenging ◽  
Docking Studies ◽  
Antimicrobial Compounds ◽  
Molecular Docking Studies ◽  
Fungal Strains ◽  
Chemical Structures

Background: The 1,4-naphthoquinone ring has attracted prominent interest in the field of medicinal chemistry due to its potent pharmacological activity as antioxidant, antibacterial, antifungal, and anticancer. Objective: Herein, a series of new Schiff bases (4-6) and chalcones (8a-c & 9a-d) bearing 1,4-naphthoquinone moiety were synthesized in good yields and were subjected to in-vitro antimicrobial, antioxidant, and molecular docking testing. Methods: A facile protocol has been described in this study for the synthesis of new derivatives (4-7, 8a-c, and 9a-d) bearing 1,4-naphthoquinone moiety. The chemical structures of all the synthesized compounds were identified by 1H-NMR, 13C-NMR, MS, and elemental analyses. Moreover, these derivatives were assessed for their in-vitro antimicrobial activity against gram-positive, gram-negative bacteria, and fungal strains. Further studies were conducted to test their antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay. Molecular docking studies were realized to identify the most likely interactions of the novel compounds within the protein receptor. Results: The antimicrobial results showed that most of the compounds displayed good efficacy against both bacterial and fungal strains. The antioxidant study revealed that compounds 9d, 9a, 9b, 8c, and 6 exhibited the highest radical scavenging activity. Docking studies of the most active antimicrobial compounds within GLN- 6-P, recorded good scores with several binding interactions with the active sites. Conclusion: Based on the obtained results, it was found that compounds 8b, 9b, and 9c displayed the highest activity against both bacterial and fungal strains. The obtained findings from the DPPH radical scavenging method revealed that compounds 9d and 9a exhibited the strongest scavenging potential. The molecular docking studies proved that the most active antimicrobial compounds 8b, 9b and 9c displayed the highest energy binding scores within the glucosamine-6-phosphate synthase (GlcN-6-P) active site.

scholarly journals Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Acetyl Cysteine

<p><b>To</b></p> <p><b>Respected Sir/Madam</b> </p> <p>Chemarxiv</p> <p> </p> <p><b>Respected Sir/Madam</b> </p> <p> </p> <p><b>Sub</b>: submission of preprint of article to Chemarxiv for online publication.</p> <p> </p> <p>I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”.</p> <p> </p> <p>In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol<sup>-1</sup> while for hydroxychloroquine it is -6.66 kcal mol<sup>-1</sup>. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine.</p> <p>I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. </p> <p>Thanking you</p> <p> </p> <p>With regards</p> <p>Roopa Guthappa</p> <p><a href="mailto:[email protected]">[email protected]</a></p>

scholarly journals Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Acetyl Cysteine

<p><b>To</b></p> <p><b>Respected Sir/Madam</b> </p> <p>Chemarxiv</p> <p> </p> <p><b>Respected Sir/Madam</b> </p> <p> </p> <p><b>Sub</b>: submission of preprint of article to Chemarxiv for online publication.</p> <p> </p> <p>I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”.</p> <p> </p> <p>In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol<sup>-1</sup> while for hydroxychloroquine it is -6.66 kcal mol<sup>-1</sup>. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine.</p> <p>I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. </p> <p>Thanking you</p> <p> </p> <p>With regards</p> <p>Roopa Guthappa</p> <p><a href="mailto:[email protected]">[email protected]</a></p>

scholarly journals Design, synthesis, antimicrobial evaluation, and molecular docking studies of novel symmetrical 2,5‐difunctionalized 1,3,4‐oxadiazoles

2019 ◽  
Vol 57 (3) ◽  
pp. 1044-1054 ◽  
Author(s):  
Shaima Hkiri ◽  
Afifa Hafidh ◽  
Jean‐François Cavalier ◽  
Soufiane Touil ◽  
Ali Samarat
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Antimicrobial Evaluation

scholarly journals Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

2020 ◽  
Vol 32 (5) ◽  
pp. 1151-1157 ◽  
Author(s):  
P. Raghurama Shetty ◽  
G. Shivaraja ◽  
G. Krishnaswamy ◽  
K. Pruthviraj ◽  
Vivek Chandra Mohan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Active Sites ◽  
Docking Studies ◽  
Spectrometric Analysis ◽  
Molecular Docking Studies ◽  
In Vitro Investigation

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

scholarly journals Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis

Toxins ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 181 ◽  
Author(s):  
Samuel Kwofie ◽  
Bismark Dankwa ◽  
Kweku Enninful ◽  
Courage Adobor ◽  
Emmanuel Broni ◽  
...  
Keyword(s):  
Wound Healing ◽  
Molecular Docking ◽  
Mast Cells ◽  
Binding Energy ◽  
Buruli Ulcer ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Granule Exocytosis ◽  
Molecular Docking Studies ◽  
Healing Processes

Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Wound healing processes involve activation of the blood platelets to release the contents of the dense granules mainly serotonin, calcium ions, and ADP/ATP by exocytosis into the bloodstream. The serotonin release results in attracting more platelets and mast cells to the wound site, with the mast cells also undergoing degranulation, releasing compounds into the bloodstream by exocytosis. Recent work has identified interference in the co-translational translocation of many secreted proteins via the endoplasmic reticulum and cell death involving Wiskott-Aldrich syndrome protein (WASP), Sec61, and angiotensin II receptors (AT2R). We hypothesized that mycolactone by being lipophilic, passively crosses cell membranes and binds to key proteins that are involved in exocytosis by platelets and mast cells, thus inhibiting the initiation of wound healing processes. Based on this, molecular docking studies were performed with mycolactone against key soluble n-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and regulators, namely Vesicle-associated membrane protein (VAMP8), Synaptosomal-associated protein (SNAP23, syntaxin 11, Munc13-4 (its isoform Munc13-1 was used), and Munc18b; and also against known mycolactone targets (Sec61, AT2R, and WASP). Munc18b was shown to be a plausible mycolactone target after the molecular docking studies with binding affinity of −8.5 kcal/mol. Structural studies and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding energy calculations of the mycolactone and Munc18b complex was done with 100 ns molecular dynamics simulations using GROMACS. Mycolactone binds strongly to Munc18b with an average binding energy of −247.571 ± 37.471 kJ/mol, and its presence elicits changes in the structural conformation of the protein. Analysis of the binding interactions also shows that mycolactone interacts with Arg405, which is an important residue of Munc18b, whose mutation could result in impaired granule exocytosis. These findings consolidate the possibility that Munc18b could be a target of mycolactone. The implication of the interaction can be experimentally evaluated to further understand its role in granule exocytosis impairment in Buruli ulcer.

Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 560-568
Author(s):  
Vijayan R. Akhila ◽  
Maheswari R. Priya ◽  
Daisy R. Sherin ◽  
Girija K. Krishnapriya ◽  
Sreerekha V. Keerthi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mechanochemical Synthesis ◽  
Active Sites ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Antidiabetic Agents ◽  
Molecular Docking Studies ◽  
Ic50 Value

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by &#945;-glucosidase and &#945;-amylase inhibition assays. The, IC50 value for &#945;-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 &#181;M and the IC50 value for &#945;-amylase inhibition, 195.03 &#181;M, whereas the corresponding values for reference acarbose were 53.38 &#181;M and 502.03 &#181;M, respectively. Molecular docking studies at the active sites of &#945;- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for &#945;-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

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