Synthesis, DFT Characterization and In Silico Evaluation of 1-(4-Methylpiperazin-1-yl-methyl)-3-benzyl-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (MBHT)

Abstract

In this study, the compound 1-(4-methylpiperazin-1-yl-methyl)-3-benzyl-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (MBHT), synthesized using the Mannich reaction, was comprehensively investigated using theoretical methods. The stable geometry of the molecule was optimized using the B3LYP and B3PW91 functionals within the framework of density functional theory (DFT) and with the basis set 6-311G(d,p). Structural characterization was performed by determining the functional groups using FT-IR spectroscopy and by detailed investigation of the proton and carbon environments using 1H-NMR and 13C-NMR spectroscopies. Theoretical IR and NMR data were calculated using Gaussian 09W software and the GIAO method; the obtained results were validated by comparing them with experimental findings. The molecule's electronic structure was evaluated in detail through parameters such as HOMO–LUMO energy levels and energy gap, Natural Bond Orbital (NBO) analysis, nonlinear optical (NLO) properties, molecular electrostatic potential (MEP) maps, and Mulliken charge distributions. These analyses provided information about MBHT's electron distribution, reactivity profile, and potential interaction sites. Furthermore, molecular docking studies were performed using PDB:5HS1 and PDB:5EQB proteins to investigate its in-silico potential for biological interaction with candidiasis. In the final part of the study, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis was conducted to evaluate MBHT as a drug candidate. The findings reveal both the structural and electronic properties of MBHT, as well as its potential for interaction with biological targets, providing important information regarding the compound's suitability for the drug development process.

Keywords

• 1
• 2
• 4-Triazolone derivatives
• Mannich reaction
• DFT calculations
• HOMO–LUMO
• Molecular docking.

1-(4-Metilpiperazin-1-il-metil)-3-benzil-4-(4-hidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on (MBHT)'nin Sentezi, DFT Karakterizasyonu ve Bilgisayar Destekli Değerlendirilmesi

Abstract

Bu çalışmada, Mannich reaksiyonu kullanılarak sentezlenen 1-(4-metilpiperazin-1-il-metil)-3-benzil-4-(4-hidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on (MBHT) bileşiği, teorik yöntemlerle kapsamlı bir şekilde incelenmiştir. Molekülün kararlı geometrisi, yoğunluk fonksiyoneli teorisi (DFT) kapsamında B3LYP ve B3PW91 fonksiyonelleri kullanılarak ve 6-311G(d,p) temel seti ile optimize edilmiştir. Yapısal karakterizasyon, FT-IR spektroskopisi ile fonksiyonel grupların belirlenmesi ve 1H-NMR ile 13C-NMR spektroskopileri ile proton ve karbon ortamlarının ayrıntılı incelenmesi yoluyla gerçekleştirilmiştir. Teorik IR ve NMR verileri, Gaussian 09W yazılımı ve GIAO yöntemi ile hesaplanmış; elde edilen sonuçlar deneysel bulgularla karşılaştırılarak doğrulanmıştır. Molekülün elektronik yapısı, HOMO–LUMO enerji seviyeleri ve enerji boşluğu, Doğal Bağ Orbitali (NBO) analizi, doğrusal olmayan optik (NLO) özellikleri, moleküler elektrostatik potansiyel (MEP) haritaları ve Mulliken yük dağılımları gibi parametreler üzerinden detaylı bir şekilde değerlendirilmiştir. Bu analizler, MBHT’nin elektron dağılımı, reaktivite profili ve potansiyel etkileşim bölgeleri hakkında bilgi sağlamıştır. Ayrıca, kandidiyazis hastalığına yönelik biyolojik etkileşim in-siliko potansiyelini incelemek amacıyla PDB:5HS1 ve PDB: 5EQB proteinleri kullanılarak moleküler docking çalışmaları gerçekleştirilmiştir. Çalışmanın son bölümünde, MBHT bileşiğinin ilaç adayı olarak değerlendirilmesi için ADMET (absorpsiyon, dağılım, metabolizma, atılım ve toksisite) analizi yapılmıştır. Elde edilen bulgular, MBHT’nin hem yapısal hem de elektronik özelliklerinin yanı sıra biyolojik hedeflerle etkileşim potansiyelini ortaya koyarak, bileşiğin ilaç geliştirme sürecindeki uygunluğuna yönelik önemli bilgiler sunmaktadır.

Keywords

• 1
• 2
• 4-Triazol türevleri
• Mannich reaksiyonu
• DFT hesaplamaları
• HOMO–LUMO
• Moleküler Docking.

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