Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents

Abstract 4-Aminocoumarins are significant in organic synthesis as key building blocks for various heterocyclic structures with pharmacological importance. This study focuses on synthesizing phenyliodonium derivatives of 4-aminocoumarins (T1-T6) and evaluating their broad-spectrum biological properti...

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Main Authors: Serin Zachariah, Shiji T. M, Kannan Vadakkadath Meethal, Sara Jones, T. V. Suchithra
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95078-8
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author Serin Zachariah
Shiji T. M
Kannan Vadakkadath Meethal
Sara Jones
T. V. Suchithra
author_facet Serin Zachariah
Shiji T. M
Kannan Vadakkadath Meethal
Sara Jones
T. V. Suchithra
author_sort Serin Zachariah
collection DOAJ
description Abstract 4-Aminocoumarins are significant in organic synthesis as key building blocks for various heterocyclic structures with pharmacological importance. This study focuses on synthesizing phenyliodonium derivatives of 4-aminocoumarins (T1-T6) and evaluating their broad-spectrum biological properties, including antibacterial, antifungal, antiviral, antioxidant, cytotoxicity, and wound-healing properties. The compounds synthesized were structurally confirmed through UV-Vis, GC-MS, 1H-NMR, 13C-NMR, FT-IR, melting point, and CHNS analysis. The in vitro antibacterial and antifungal activities of these compounds were assessed against eight bacterial strains and five plant fungal pathogens. The antiviral property was evaluated by measuring the reduction in cytopathic effects of Dengue virus type-2 in BHK-21 cells. Cytotoxicity testing on human epidermal keratinocyte cells using the MTT assay at concentrations ranging from 1 to 100 µg/mL revealed that none of the compounds exhibited significant cytotoxic effects. Additionally, ADME/Toxicity, molecular docking, antioxidant, and wound-healing studies were examined, further supporting the therapeutic potential of these compounds. Most of the synthesized phenyliodonium derivatives demonstrated broad-spectrum antibacterial and antifungal activities. Among them, Compound T6 exhibited the most potent antimicrobial activity, as indicated by its MIC₉₀ and MBC values, demonstrating superior efficacy compared to ciprofloxacin. The antiviral test against Dengue virus type-2 showed minimal effects with a cytopathic effect reduction of 10–13% at non-toxic concentrations. These compounds exhibited broad-spectrum antimicrobial activity coupled with minimal cytotoxicity, highlighting their potential as promising candidates for developing novel therapeutic agents.
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spelling doaj-art-88b2f77012eb4e7ca6fcb9b2fab7ab082025-08-20T03:03:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111910.1038/s41598-025-95078-8Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agentsSerin Zachariah0Shiji T. M1Kannan Vadakkadath Meethal2Sara Jones3T. V. Suchithra4Department of Bioscience and Engineering, National Institute of TechnologyDivision of Biochemistry and Molecular Biology, Department of Zoology, University of CalicutDivision of Biochemistry and Molecular Biology, Department of Zoology, University of CalicutPathogen Biology Group, Rajiv Gandhi Centre for BiotechnologyDepartment of Bioscience and Engineering, National Institute of TechnologyAbstract 4-Aminocoumarins are significant in organic synthesis as key building blocks for various heterocyclic structures with pharmacological importance. This study focuses on synthesizing phenyliodonium derivatives of 4-aminocoumarins (T1-T6) and evaluating their broad-spectrum biological properties, including antibacterial, antifungal, antiviral, antioxidant, cytotoxicity, and wound-healing properties. The compounds synthesized were structurally confirmed through UV-Vis, GC-MS, 1H-NMR, 13C-NMR, FT-IR, melting point, and CHNS analysis. The in vitro antibacterial and antifungal activities of these compounds were assessed against eight bacterial strains and five plant fungal pathogens. The antiviral property was evaluated by measuring the reduction in cytopathic effects of Dengue virus type-2 in BHK-21 cells. Cytotoxicity testing on human epidermal keratinocyte cells using the MTT assay at concentrations ranging from 1 to 100 µg/mL revealed that none of the compounds exhibited significant cytotoxic effects. Additionally, ADME/Toxicity, molecular docking, antioxidant, and wound-healing studies were examined, further supporting the therapeutic potential of these compounds. Most of the synthesized phenyliodonium derivatives demonstrated broad-spectrum antibacterial and antifungal activities. Among them, Compound T6 exhibited the most potent antimicrobial activity, as indicated by its MIC₉₀ and MBC values, demonstrating superior efficacy compared to ciprofloxacin. The antiviral test against Dengue virus type-2 showed minimal effects with a cytopathic effect reduction of 10–13% at non-toxic concentrations. These compounds exhibited broad-spectrum antimicrobial activity coupled with minimal cytotoxicity, highlighting their potential as promising candidates for developing novel therapeutic agents.https://doi.org/10.1038/s41598-025-95078-8SynthesisCoumarin derivativesADME/ToxicityAntimicrobialMolecular dockingScratch wound assay
spellingShingle Serin Zachariah
Shiji T. M
Kannan Vadakkadath Meethal
Sara Jones
T. V. Suchithra
Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
Scientific Reports
Synthesis
Coumarin derivatives
ADME/Toxicity
Antimicrobial
Molecular docking
Scratch wound assay
title Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
title_full Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
title_fullStr Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
title_full_unstemmed Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
title_short Synthesis, biological evaluation, pharmacological profiling, and molecular docking studies of 4-Aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
title_sort synthesis biological evaluation pharmacological profiling and molecular docking studies of 4 aminocoumarin based phenyliodonium derivatives as potent therapeutic agents
topic Synthesis
Coumarin derivatives
ADME/Toxicity
Antimicrobial
Molecular docking
Scratch wound assay
url https://doi.org/10.1038/s41598-025-95078-8
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