Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach

This study utilized in vitro and in silico methods to assess the antifungal efficacy of synthesized pyrazoline derivatives (4a–e) against Candida species. The compounds were produced by a one-pot process and structurally analyzed using spectroscopic methods. The antifungal efficacy was evaluated aga...

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Main Authors: Muhammad Rohim, Yuli Haryani, Neni Frimayanti, Fauzan Zein Muttaqin, Hilwan Yuda Teruna, Rudi Hendra
Format: Article
Language:English
Published: Department of Chemistry, Universitas Gadjah Mada 2025-07-01
Series:Indonesian Journal of Chemistry
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Online Access:https://jurnal.ugm.ac.id/ijc/article/view/105255
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author Muhammad Rohim
Yuli Haryani
Neni Frimayanti
Fauzan Zein Muttaqin
Hilwan Yuda Teruna
Rudi Hendra
author_facet Muhammad Rohim
Yuli Haryani
Neni Frimayanti
Fauzan Zein Muttaqin
Hilwan Yuda Teruna
Rudi Hendra
author_sort Muhammad Rohim
collection DOAJ
description This study utilized in vitro and in silico methods to assess the antifungal efficacy of synthesized pyrazoline derivatives (4a–e) against Candida species. The compounds were produced by a one-pot process and structurally analyzed using spectroscopic methods. The antifungal efficacy was evaluated against C. albicans, C. glabrata, and C. krusei using minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) assays. Among the derivatives, compound 4e exhibited potent antifungal action, displaying MIC values similar to ketoconazole. Molecular docking and pharmacophore modeling have shown that 4e interacts efficiently with critical residues of lanosterol 14α-demethylase (CYP51). The density functional theory (DFT) study indicated advantageous electrical characteristics, while molecular dynamics simulations validated the structural stability of the 4e–CYP51 complex, evidenced by low RMSD and RMSF values, along with an MM/GBSA binding energy comparable to that of ketoconazole. A robust association between binding energy and MIC substantiates the predictive use of computational data. The results suggest that compound 4e replicates the binding characteristics of ketoconazole and may be a viable candidate for antifungal medication development. This integrative strategy reinforces the justification for additional optimization and preclinical assessment of pyrazoline-based antifungal drugs aimed at CYP51.
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spelling doaj-art-f3e745282d2b4e9595885dea03ad4ea52025-08-20T03:01:41ZengDepartment of Chemistry, Universitas Gadjah MadaIndonesian Journal of Chemistry1411-94202460-15782025-07-012541226124310.22146/ijc.10525537824Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> ApproachMuhammad Rohim0Yuli Haryani1Neni Frimayanti2Fauzan Zein Muttaqin3Hilwan Yuda Teruna4Rudi Hendra5Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Riau, Kampus Binawidya, Jl. HR. Soebrantas Km. 12.5, Simpang Baru, Tampan, Pekanbaru, Riau 28293, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Riau, Kampus Binawidya, Jl. HR. Soebrantas Km. 12.5, Simpang Baru, Tampan, Pekanbaru, Riau 28293, IndonesiaDepartment of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Jl. Kamboja, Simpang Baru, Tampan, Pekanbaru, Riau 28293, IndonesiaFaculty of Pharmacy, Bhakti Kencana University, Jl. Soekarno Hatta No. 754, Bandung 40614, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Riau, Kampus Binawidya, Jl. HR. Soebrantas Km. 12.5, Simpang Baru, Tampan, Pekanbaru, Riau 28293, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Riau, Kampus Binawidya, Jl. HR. Soebrantas Km. 12.5, Simpang Baru, Tampan, Pekanbaru, Riau 28293, IndonesiaThis study utilized in vitro and in silico methods to assess the antifungal efficacy of synthesized pyrazoline derivatives (4a–e) against Candida species. The compounds were produced by a one-pot process and structurally analyzed using spectroscopic methods. The antifungal efficacy was evaluated against C. albicans, C. glabrata, and C. krusei using minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) assays. Among the derivatives, compound 4e exhibited potent antifungal action, displaying MIC values similar to ketoconazole. Molecular docking and pharmacophore modeling have shown that 4e interacts efficiently with critical residues of lanosterol 14α-demethylase (CYP51). The density functional theory (DFT) study indicated advantageous electrical characteristics, while molecular dynamics simulations validated the structural stability of the 4e–CYP51 complex, evidenced by low RMSD and RMSF values, along with an MM/GBSA binding energy comparable to that of ketoconazole. A robust association between binding energy and MIC substantiates the predictive use of computational data. The results suggest that compound 4e replicates the binding characteristics of ketoconazole and may be a viable candidate for antifungal medication development. This integrative strategy reinforces the justification for additional optimization and preclinical assessment of pyrazoline-based antifungal drugs aimed at CYP51.https://jurnal.ugm.ac.id/ijc/article/view/105255antifungal activitycandida speciesmolecular dockingpyrazoline derivativesstructure-activity relationship (sar)
spellingShingle Muhammad Rohim
Yuli Haryani
Neni Frimayanti
Fauzan Zein Muttaqin
Hilwan Yuda Teruna
Rudi Hendra
Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
Indonesian Journal of Chemistry
antifungal activity
candida species
molecular docking
pyrazoline derivatives
structure-activity relationship (sar)
title Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
title_full Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
title_fullStr Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
title_full_unstemmed Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
title_short Design, Synthesis, and Antifungal Analysis of Pyrazoline Derivatives Against <i>Candida</i> Species: A Comprehensive <i>In Vitro</i> and <i>In Silico</i> Approach
title_sort design synthesis and antifungal analysis of pyrazoline derivatives against i candida i species a comprehensive i in vitro i and i in silico i approach
topic antifungal activity
candida species
molecular docking
pyrazoline derivatives
structure-activity relationship (sar)
url https://jurnal.ugm.ac.id/ijc/article/view/105255
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