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

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.

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

10.21203/rs.2.22295/v3 ◽

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.

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

10.21203/rs.2.22295/v2 ◽

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.

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

Anti-Infective Agents ◽

10.2174/2211352517666190627144315 ◽

2020 ◽

Vol 18 (3) ◽

pp. 306-314 ◽

Cited By ~ 2

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.

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Design, Synthesis and Biological Potential of 5-(2-Amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol Scaffolds as Promising Antimicrobial and Anticancer Agents

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557518666181009141924 ◽

2019 ◽

Vol 19 (10) ◽

pp. 851-864 ◽

Cited By ~ 1

Author(s):

Sanjiv Kumar ◽

Balasubramanian Narasimhan ◽

Siong Meng Lim ◽

Kalavathy Ramasamy ◽

Vasudevan Mani ◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Docking Study ◽

Binding Pocket ◽

Dilution Method ◽

Molecular Docking Study ◽

Design Synthesis ◽

Biological Potential

Background: A series of 5-(2-amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol scaffolds was synthesized by Claisen-Schmidt condensation and characterized by NMR, IR, Mass and elemental analyses. Methods: The synthesized pyrimidine scaffolds were screened for their antimicrobial activity by tube dilution method as well for antiproliferative activity (human colorectal (HCT116) cancer cell line) by SRB assay. Results: The antimicrobial screening results demonstrated that compounds, k6, k12, k14 and k20 were found to be the most potent ones against selected microbial species. The anticancer screening results indicated that compounds, k8 and k14 displayed potent anticancer activity against cancer cell line (HCT116). Conclusion: Further, the molecular docking study carried to find out the interaction between active pyrimidine compounds with CDK-8 protein indicated that compound k14 showed best dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

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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

Medicinal Chemistry ◽

10.2174/1573406415666190724142951 ◽

2020 ◽

Vol 16 (7) ◽

pp. 892-902 ◽

Cited By ~ 3

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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