Synthesis, Biological Evaluation and Molecular Docking Study of Pyrazole, Pyrazoline Clubbed Pyridine as Potential Antimicrobial Agents

2020 ◽  
Vol 18 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Nisheeth C. Desai ◽  
Darshita V. Vaja ◽  
Krunalsinh A. Jadeja ◽  
Surbhi B. Joshi ◽  
Vijay M. Khedkar
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Biological Evaluation ◽  
Mass Spectral Data ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Chemical Structures ◽  
Subunit B

Introduction: In continuation of our efforts to find new antimicrobials, herein we report the synthesis of various pyrazole, pyrazoline, and pyridine based novel bioactive heterocycles (3a-t). Methods: Newly synthesized compounds were analysed for their antimicrobial activity. Compounds 3c, 3h, 3i, 3k, 3n, and 3q showed significant antimicrobial activity. Results: Molecular docking study for the most active analogues against DNA gyrase subunit b (PDB ID: 1KZN) corroborated well with the observed antimicrobial potency exhibiting significant binding affinity. Conclusion: Interpretation of the chemical structures reported in this paper was based on IR, 1H NMR, 13C NMR, and mass spectral data.

scholarly journals Synthesis, characterization, synergistic antimicrobial properties and molecular docking of sugar modified uridine derivatives

2021 ◽  
Vol 32 (1) ◽  
pp. 6-21
Author(s):  
Jannatul Maowa ◽  
Asraful Alam ◽  
Kazi M. Rana ◽  
Sujan Dey ◽  
Anowar Hosen ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Density Functional ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Docking Study ◽  
Bacterial Strains ◽  
Molecular Docking Study ◽  
Antibacterial And Antifungal Activities

Abstract Nucleosides and their analogues are an important, well-established class of clinically useful medicinal agents that exhibit antiviral and anticancer activity. Thus, our research group has focused on the synthesis of new nucleoside derivatives that could be tested for their broad-spectrum biological activity. In this study, two new series of nucleoside derivatives were synthesized from uridine (1) through facile two-step reactions using the direct acylation method, affording 5’-O-acyl uridine derivatives in good yields. The isolated uridine analogs were further transformed into two series of 2’,3’-di-O-acyl derivatives bearing a wide variety of functionalities in a single molecular framework to evaluate their antimicrobial activity. The new synthesized compounds were characterized through physicochemical, elemental and spectroscopic analysis, and all were screened for their in vitro antimicrobial activity against selected human and plant pathogenic strains. The test compounds revealed moderate to good antibacterial and antifungal activities and were more effective against fungal phytopathogens than against bacterial strains, while many of them exhibited better antimicrobial activity than standard antibiotics. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests against all microorganisms were also conducted for five compounds based on their activity (6, 11, 13, 16, and 17). In addition, all the derivatives were optimized using density functional theory (DFT) B3LYP/6-31g+(d,p) calculations to elucidate their thermal and molecular orbital properties. A molecular docking study was performed using the human protein 5WS1 to predict their binding affinity and modes, and ADMET and SwissADME calculations confirmed the improved pharmacokinetic properties of the compounds. Besides, structure–activity relationship (SAR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) studies were also performed. Thus, the improvement of the bioactivity of these compounds is expected to significantly contribute to the design of more antimicrobial agents for therapeutic use in the future.

Tetrazoloquinoline-1,2,3-Triazole Derivatives as Antimicrobial Agents: Synthesis, Biological Evaluation and Molecular Docking Study

2020 ◽  
pp. 1-22
Author(s):  
Mubarak H. Shaikh ◽  
Dnyaneshwar D. Subhedar ◽  
Satish V. Akolkar ◽  
Amol A. Nagargoje ◽  
Vijay M. Khedkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Triazole Derivatives

scholarly journals DESIGN, INSILICO SCREENING, MOLECULAR DOCKING, SYNTHESIS AND BIOLOGICAL EVALUATION OF BENZO-FUSED FIVE MEMBERED NITROGEN CONTAINING HETEROCYCLE AGAINST DNA GYRASE SUBUNIT B AS POTENTIAL ANTIMICROBIAL AGENT

2021 ◽  
Vol 10 (3) ◽  
pp. 3016-3023
Author(s):  
Tejaswini D Patil
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Rapid Development ◽  
Dna Gyrase ◽  
Docking Study ◽  
Biological Evaluation ◽  
Antimicrobial Drug ◽  
Antimicrobial Drugs ◽  
Antimicrobial Drug Resistance ◽  
Subunit B

Because of its function in DNA replication, DNA gyrase subunit B (1KZN) is a promising target for antimicrobial drug development. There is an urgent requirement for the designing and improvement of novel antimicrobial drugs due to the rapid development of antimicrobial drug resistance. The aim of this study is to use molecular docking to design, synthesise, and identify benzo-fused five-membered nitrogen containing heterocycle against DNA gyrase subunit B (1KZN). Using an effective procedure, 2-(1H-1,2,3-Benzotriazol-1-yl)-N-substituted acetamide was synthesised based on the literature review. The antimicrobial activity of all synthesised compounds was tested against four different organisms: E. coli, P. aeruginosa, S. aureus, and Candida albicans. The compound binds to the active site of DNA gyrase subunit B (1KZN) in a docking study, indicating that it may have antimicrobial activity. The compounds BT4 and BT6 have the antimicrobial capacity, according to the findings of this report. BT3 has the ability to be an antibacterial agent for Staphylococcus aureus.

scholarly journals Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives

2020 ◽  
Author(s):  
Harsh Kumar ◽  
Aakash Deep ◽  
Rakesh Kumar Marwaha
Keyword(s):  
Molecular Docking ◽  
Radical Scavenging ◽  
Docking Study ◽  
Binding Pocket ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Biological Potential ◽  
In Silico Studies

Abstract Background: Looking at the extensive range of biological potential of thiazolidine-2,4-dione (TZD) moiety, a new series of thiazolidine-2,4-dione analogues was synthesized. Different spectral techniques (1H-NMR, IR, MS etc.) were used to confirm the chemical structures of the synthesized analogues. These synthesized compounds were then screened for their antioxidant and antimicrobial potential.Results and discussion: The antimicrobial screening was carried out against selected strains of fungi and bacteria using serial tube dilution method. The antioxidant potential was assessed using stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Further, the interaction between synthesized thiazolidine-2,4-dione compounds and DNA gyrase was explored using molecular docking studies. Various ADME parameters were also studied to evaluate the drug likeness of the synthesized compounds. Conclusion: In antimicrobial evaluation, the compounds 4, 9, 11, 12, 13, 15 and 16 displayed promising activity against selected strains of microbes. Antioxidant evaluation found compound 6 having IC50 = 9.18 μg/mL to be the most potent compound in the series. The molecular docking study revealed compounds 4 (dock score = -4.73) and 7 (dock score = -4.61) with decent docking score possess good interaction inside the ATP binding pocket and therefore can be used as lead structure for further optimizing into potent antimicrobial molecule.

scholarly journals Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives

2020 ◽  
Author(s):  
Harsh Kumar ◽  
Aakash Deep ◽  
Rakesh Kumar Marwaha
Keyword(s):  
Molecular Docking ◽  
Radical Scavenging ◽  
Dna Gyrase ◽  
Docking Study ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Biological Potential ◽  
In Silico Studies

Abstract Background : Looking at the extensive biological potential of thiazolidine-2,4-dione (TZD) moiety, a new series of thiazolidine-2,4-dione analogues was synthesized. Different spectral techniques ( 1 H-NMR, IR, MS etc.) were used to confirm the chemical structures of the synthesized analogues. These synthesized compounds were screened for their antioxidant and antimicrobial potential. Results and discussion : The antimicrobial screening was carried out against selected strains of fungi and bacteria using serial tube dilution method. The antioxidant potential was assessed using stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Further, the interaction between synthesized thiazolidine-2,4-dione compounds and DNA gyrase was explored using molecular docking studies. Various ADME parameters were also studied to evaluate the drug likeness of the synthesized compounds. Conclusion: In antimicrobial evaluation, the compounds 4 , 9 , 11 , 12, 13 , 15 and 16 displayed promising activity against selected strains of microbes. Antioxidant evaluation found compound 6 having IC 50 = 9.18 μg/mL to be the most potent compound in the series. The molecular docking study revealed compounds 4 ( dock score = -4.73) and 7 (dock score = -4.61) with decent docking score, possess good interaction inside the ATP binding pocket of DNA gyrase and therefore can be used as lead structure for further optimizing into potent antimicrobial molecule.

scholarly journals Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives

2020 ◽  
Author(s):  
Harsh Kumar ◽  
Aakash Deep ◽  
Rakesh Kumar Marwaha
Keyword(s):  
Molecular Docking ◽  
Radical Scavenging ◽  
Dna Gyrase ◽  
Docking Study ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Biological Potential ◽  
In Silico Studies

Abstract Background: Looking at the extensive biological potential of thiazolidine-2,4-dione (TZD) moiety, a new series of thiazolidine-2,4-dione analogues was synthesized. Different spectral techniques (1H-NMR, IR, MS etc.) were used to confirm the chemical structures of the synthesized analogues. These synthesized compounds were screened for their antioxidant and antimicrobial potential. Results and discussion: The antimicrobial screening was carried out against selected strains of fungi and bacteria using serial tube dilution method. The antioxidant potential was assessed using stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Further, the interaction between synthesized thiazolidine-2,4-dione compounds and DNA gyrase was explored using molecular docking studies. Various ADME parameters were also studied to evaluate the drug likeness of the synthesized compounds. Conclusion: In antimicrobial evaluation, the compounds 4, 9, 11, 12, 13, 15 and 16 displayed promising activity against selected strains of microbes. Antioxidant evaluation found compound 6 having IC50 = 9.18 μg/mL to be the most potent compound in the series. The molecular docking study revealed compounds 4 (dock score = -4.73) and 7 (dock score = -4.61) with decent docking score, possess good interaction inside the ATP binding pocket of DNA gyrase and therefore can be used as lead structure for further optimizing into potent antimicrobial molecule.

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones

2019 ◽  
Vol 15 (6) ◽  
pp. 659-675
Author(s):  
Mohamed F. Zayed ◽  
Sabrin R.M. Ibrahim ◽  
EL-Sayed E. Habib ◽  
Memy H. Hassan ◽  
Sahar Ahmed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Receptor Site ◽  
Docking Study ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Active Compounds ◽  
Highly Active ◽  
Strong Binding ◽  
Agar Disc

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities. Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities. Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding. Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding. Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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