Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis

This study reports the synthesis and characterization of a novel series of 5-nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives (5a-5v) obtained through the reaction of 3-chloro-5-nitro-N-phenyl-1H-indazole-1-carboxamide (4) with diverse aniline derivatives in isopropanol. The comp...

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Main Authors: Mithlesh Yadav, Suraj N. Mali, Bharti Sharma, Haya Yasin, Rohit Pal, Gurubasavaraja Swamy Purawarga Matada, Archana Kapoor
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Chemical Physics Impact
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667022424002494
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author Mithlesh Yadav
Suraj N. Mali
Bharti Sharma
Haya Yasin
Rohit Pal
Gurubasavaraja Swamy Purawarga Matada
Archana Kapoor
author_facet Mithlesh Yadav
Suraj N. Mali
Bharti Sharma
Haya Yasin
Rohit Pal
Gurubasavaraja Swamy Purawarga Matada
Archana Kapoor
author_sort Mithlesh Yadav
collection DOAJ
description This study reports the synthesis and characterization of a novel series of 5-nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives (5a-5v) obtained through the reaction of 3-chloro-5-nitro-N-phenyl-1H-indazole-1-carboxamide (4) with diverse aniline derivatives in isopropanol. The compounds underwent thorough biological evaluation encompassing antibacterial, antifungal, and in addition to antioxidant potential assessed through DPPH (IC50 = 0.105-0.513 μmol/mL) and ABTS assays (IC50 = 0.124-0.538 μmol/mL). Remarkably, compound 5b displayed exceptional antibacterial efficacy, while compounds 5k, 5p, and 5q exhibited noteworthy antifungal potential. Compound 5k showed the most significant antioxidant activity. Molecular docking studies unveiled robust binding interactions with target enzymes (PDB ID: 3SRG), and molecular dynamics simulations indicated the stability of the most active compound at the binding site. Additionally, favourable drug-likeness and ADMET properties underscore the promising therapeutic potential of these derivatives, urging further investigations for potential clinical applications. The multifaceted activities, including antibacterial, antifungal, and antioxidant properties, make these derivatives compelling candidates for in-depth exploration in the pursuit of novel therapeutic agents.
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spelling doaj-art-11de1dff598042a98ed188f2bdaac63d2025-08-20T02:48:39ZengElsevierChemical Physics Impact2667-02242024-12-01910070510.1016/j.chphi.2024.100705Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysisMithlesh Yadav0Suraj N. Mali1Bharti Sharma2Haya Yasin3Rohit Pal4Gurubasavaraja Swamy Purawarga Matada5Archana Kapoor6Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, IndiaSchool of Pharmacy, D. Y. Patil University (Deemed to be University), Navi Mumbai, Maharashtra, IndiaDepartment of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates; Corresponding author at: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates.Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, Karnataka, IndiaIntegrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, Karnataka, IndiaDepartment of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India; Corresponding author at: Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, Haryana-125001, India.This study reports the synthesis and characterization of a novel series of 5-nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives (5a-5v) obtained through the reaction of 3-chloro-5-nitro-N-phenyl-1H-indazole-1-carboxamide (4) with diverse aniline derivatives in isopropanol. The compounds underwent thorough biological evaluation encompassing antibacterial, antifungal, and in addition to antioxidant potential assessed through DPPH (IC50 = 0.105-0.513 μmol/mL) and ABTS assays (IC50 = 0.124-0.538 μmol/mL). Remarkably, compound 5b displayed exceptional antibacterial efficacy, while compounds 5k, 5p, and 5q exhibited noteworthy antifungal potential. Compound 5k showed the most significant antioxidant activity. Molecular docking studies unveiled robust binding interactions with target enzymes (PDB ID: 3SRG), and molecular dynamics simulations indicated the stability of the most active compound at the binding site. Additionally, favourable drug-likeness and ADMET properties underscore the promising therapeutic potential of these derivatives, urging further investigations for potential clinical applications. The multifaceted activities, including antibacterial, antifungal, and antioxidant properties, make these derivatives compelling candidates for in-depth exploration in the pursuit of novel therapeutic agents.http://www.sciencedirect.com/science/article/pii/S26670224240024945-NitroindazoleAntimicrobial activityAntioxidant activityMolecular docking studiesMolecular dynamics simulation study
spellingShingle Mithlesh Yadav
Suraj N. Mali
Bharti Sharma
Haya Yasin
Rohit Pal
Gurubasavaraja Swamy Purawarga Matada
Archana Kapoor
Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
Chemical Physics Impact
5-Nitroindazole
Antimicrobial activity
Antioxidant activity
Molecular docking studies
Molecular dynamics simulation study
title Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
title_full Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
title_fullStr Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
title_full_unstemmed Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
title_short Synthesis, antioxidant, antimicrobial activities and molecular modeling analysis of some 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide derivatives: Docking, SAR, toxicity and molecular dynamics analysis
title_sort synthesis antioxidant antimicrobial activities and molecular modeling analysis of some 5 nitro n phenyl 3 phenylamino 1h indazole 1 carboxamide derivatives docking sar toxicity and molecular dynamics analysis
topic 5-Nitroindazole
Antimicrobial activity
Antioxidant activity
Molecular docking studies
Molecular dynamics simulation study
url http://www.sciencedirect.com/science/article/pii/S2667022424002494
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