AN IN SILICO PHARMACOKINETIC INVESTIGATION OF ORGANIC LUMINOGENS: UNDERSTANDING THE NIR AIEGENS AND THEIR INTERACTIONS WITH SERUM ALBUMINS

Harun Nalçakan; Gülbin Kurtay; Dilara Tuğçe Özdil; Züleyha Yılmaz

Makale detayları

AN IN SILICO PHARMACOKINETIC INVESTIGATION OF ORGANIC LUMINOGENS: UNDERSTANDING THE NIR AIEGENS AND THEIR INTERACTIONS WITH SERUM ALBUMINS

Yazarlar:

Harun Nalçakan | Gülbin Kurtay | Dilara Tuğçe Özdil | Züleyha Yılmaz

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.48 Issue 1, pp.56-74

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300945

pISSN:

1015-3918

Anahtar kelimeler:

Özet:

 Objective: Fluorescence imaging FLI is accepted as a highly effective method for visualizing bioanalytics directly and gaining insight into complicated biological structures and processes. In this context, newly tailored organic molecules, which have the potential to be used in FLI, especially near-infrared NIR regions supported by aggregation-induced emission luminogens AIEgens, are a rapidly developing area of study. Herein, using ADMET and molecular docking analyses, we examined the pharmacokinetic properties of both model D2-A2-D2 and newly designed Dn-An-Dn organic luminogens to interact with blood proteins, namely bovine serum albumin BSA and human serum albumin HSA, which have emerged as a versatile carrier of several therapeutic agents against preliminary cancer and infectious diseases. Material and Method: The structural properties of the examined luminogens were computed using the Gaussian 09 software package. The DFTB3LYP6-31Gd,p level was then utilized for geometry optimization and accurately determining electronic structures and molecular properties. Lipinskis rule of five was applied to predict the drugability of the compounds using the SwissADME web tool. Molinspiration was used for further validation of these properties and additional bioactivity parameters. Toxicity parameters were evaluated with OSIRIS Property Explorer v.4.5.1. Molecular docking simulations of the luminogen-albumin complexes were performed using SAMSON 2022 R2 modeling platform and implemented Autodock-vina extension. The X-ray crystal structures of bovine serum albumin BSA, PDB ID: 4F5S and human serum albumin HSA, PDB ID: 4L9Q were obtained from the Protein Data Bank. Visualization of the docking interactions was conducted using Discovery Studio Visualizer 2021. Result and Discussion: The compounds D1-A1-D1 and D1-A4-D1 stood out concerning molecular weight MW and ClogPow values, making them promising candidates for drug design. An analysis of lipophilicity revealed that these two compounds displayed high miLogP values, indicating a high degree of lipophilicity, which is generally beneficial for drug delivery. They also exhibited moderate bioactivity based on GPCR ligand and protease inhibitor PI parameters. On the other hand, D4-A3-D4 showcased paramount interaction with bovine serum albumin BSA, while D5-A3-D5 demonstrated the highest binding affinity with human serum albumin HSA.

 Objective: Fluorescence imaging FLI is accepted as a highly effective method for visualizing bioanalytics directly and gaining insight into complicated biological structures and processes. In this context, newly tailored organic molecules, which have the potential to be used in FLI, especially near-infrared NIR regions supported by aggregation-induced emission luminogens AIEgens, are a rapidly developing area of study. Herein, using ADMET and molecular docking analyses, we examined the pharmacokinetic properties of both model D2-A2-D2 and newly designed Dn-An-Dn organic luminogens to interact with blood proteins, namely bovine serum albumin BSA and human serum albumin HSA, which have emerged as a versatile carrier of several therapeutic agents against preliminary cancer and infectious diseases. Material and Method: The structural properties of the examined luminogens were computed using the Gaussian 09 software package. The DFTB3LYP6-31Gd,p level was then utilized for geometry optimization and accurately determining electronic structures and molecular properties. Lipinskis rule of five was applied to predict the drugability of the compounds using the SwissADME web tool. Molinspiration was used for further validation of these properties and additional bioactivity parameters. Toxicity parameters were evaluated with OSIRIS Property Explorer v.4.5.1. Molecular docking simulations of the luminogen-albumin complexes were performed using SAMSON 2022 R2 modeling platform and implemented Autodock-vina extension. The X-ray crystal structures of bovine serum albumin BSA, PDB ID: 4F5S and human serum albumin HSA, PDB ID: 4L9Q were obtained from the Protein Data Bank. Visualization of the docking interactions was conducted using Discovery Studio Visualizer 2021. Result and Discussion: The compounds D1-A1-D1 and D1-A4-D1 stood out concerning molecular weight MW and ClogPow values, making them promising candidates for drug design. An analysis of lipophilicity revealed that these two compounds displayed high miLogP values, indicating a high degree of lipophilicity, which is generally beneficial for drug delivery. They also exhibited moderate bioactivity based on GPCR ligand and protease inhibitor PI parameters. On the other hand, D4-A3-D4 showcased paramount interaction with bovine serum albumin BSA, while D5-A3-D5 demonstrated the highest binding affinity with human serum albumin HSA.

 Objective: Fluorescence imaging FLI is accepted as a highly effective method for visualizing bioanalytics directly and gaining insight into complicated biological structures and processes. In this context, newly tailored organic molecules, which have the potential to be used in FLI, especially near-infrared NIR regions supported by aggregation-induced emission luminogens AIEgens, are a rapidly developing area of study. Herein, using ADMET and molecular docking analyses, we examined the pharmacokinetic properties of both model D2-A2-D2 and newly designed Dn-An-Dn organic luminogens to interact with blood proteins, namely bovine serum albumin BSA and human serum albumin HSA, which have emerged as a versatile carrier of several therapeutic agents against preliminary cancer and infectious diseases. Material and Method: The structural properties of the examined luminogens were computed using the Gaussian 09 software package. The DFTB3LYP6-31Gd,p level was then utilized for geometry optimization and accurately determining electronic structures and molecular properties. Lipinskis rule of five was applied to predict the drugability of the compounds using the SwissADME web tool. Molinspiration was used for further validation of these properties and additional bioactivity parameters. Toxicity parameters were evaluated with OSIRIS Property Explorer v.4.5.1. Molecular docking simulations of the luminogen-albumin complexes were performed using SAMSON 2022 R2 modeling platform and implemented Autodock-vina extension. The X-ray crystal structures of bovine serum albumin BSA, PDB ID: 4F5S and human serum albumin HSA, PDB ID: 4L9Q were obtained from the Protein Data Bank. Visualization of the docking interactions was conducted using Discovery Studio Visualizer 2021. Result and Discussion: The compounds D1-A1-D1 and D1-A4-D1 stood out concerning molecular weight MW and ClogPow values, making them promising candidates for drug design. An analysis of lipophilicity revealed that these two compounds displayed high miLogP values, indicating a high degree of lipophilicity, which is generally beneficial for drug delivery. They also exhibited moderate bioactivity based on GPCR ligand and protease inhibitor PI parameters. On the other hand, D4-A3-D4 showcased paramount interaction with bovine serum albumin BSA, while D5-A3-D5 demonstrated the highest binding affinity with human serum albumin HSA.

 Amaç: Floresans görüntüleme FLI, biyoanalitikleri doğrudan görselleştirme ve karmaşık biyolojik yapıları ve süreçleri anlamak için son derece etkili bir yöntem olarak kabul edilir. Bu bağlamda, özellikle agregasyon-indüklü emisyon luminojenleri AIEjen tarafından desteklenen ve yakın kızılötesi NIR bölgede kullanılma potansiyeli olan yeni özelleştirilmiş organik moleküller, hızla gelişen bir çalışma alanıdır. Bu noktada, ADMET ve moleküler kenetlenme analizlerini kullanarak, hem model D2-A2-D2 hem de yeni tasarlanmış Dn-An-Dn organik luminogenlerin kan proteinleri ile etkileşme özelliklerini farmakokinetik açıdan inceledik. Bu kan proteinleri, özellikle sığır serum albumini BSA ve insan serum albumini HSA, erken kanser ve bulaşıcı hastalıklarla mücadelede çeşitli terapötik ajanların taşıyıcısı olarak öne çıkmıştır. Gereç ve Yöntem: İncelenen luminojenlerin yapısal özellikleri Gaussian 09 yazılım paketi kullanılarak hesaplandı. Daha sonra DFTB3LYP6-31Gd,p seviyesi, geometri optimizasyonu ve elektronik yapıların ve moleküler özelliklerin doğru bir şekilde belirlenmesi için kullanıldı. Bileşiklerin ilaçlaştırılabilirliğini tahmin etmek için Lipinskinin beşli kuralı SwissADME web aracı kullanılarak uygulandı. Bu özelliklerin ve ek biyoaktivite parametrelerinin daha fazla doğrulanması için Molinspiration kullanıldı. Toksisite parametreleri OSIRIS Property Explorer v.4.5.1 ile değerlendirildi. Luminojen-albümin komplekslerinin moleküler kenetlenme simülasyonları SAMSON 2022 R2 modelleme platformu ve Autodock-vina uzantısı kullanılarak gerçekleştirildi. Sığır serum albümininin BSA, PDB ID: 4F5S ve insan serum albümininin HSA, PDB ID: 4L9Q X-ışını kristal yapıları Protein Data Banktan alındı. Bağlanma etkileşimlerinin görselleştirilmesi Discovery Studio Visualizer 2021 kullanılarak gerçekleştirildi. Sonuç ve Tartışma: D1-A1-D1 ve D1-A4-D1 bileşikleri, moleküler ağırlık MA ve ClogPow değerleri açısından öne çıkarak onları ilaç tasarımı için umut verici adaylar haline getirdi. Lipofilisite analizi, bu iki bileşiğin yüksek miLogP değerleri gösterdiğini ortaya çıkardı ki bu genellikle ilaç taşınım için istenen yüksek derecede lipofilikliğe işaret etmektedir. Ayrıca bu bileşikler, GPCR ligandı ve proteaz inhibitörü PI parametrelerine dayalı olarak da orta düzeyde biyoaktivite sergilediler. Öte yandan D4-A3-D4, sığır serum albümini BSA ile olağanüstü etkileşim sergilerken, D5-A3-D5, insan serum albümini HSA ile en yüksek bağlanma afinitesini gösterdi.

Makale detayları

AN IN SILICO PHARMACOKINETIC INVESTIGATION OF ORGANIC LUMINOGENS: UNDERSTANDING THE NIR AIEGENS AND THEIR INTERACTIONS WITH SERUM ALBUMINS

Yazarlar:

Harun Nalçakan | Gülbin Kurtay | Dilara Tuğçe Özdil | Züleyha Yılmaz

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.48 Issue 1, pp.56-74

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300945

pISSN:

1015-3918

ADMET

AIEgen

BSA

HSA

molecular dockingADMET

AIEjen

BSA

HSA

moleküler kenetlenme

Sayı

Makale detayları

Yazarlar: Harun Nalçakan | Gülbin Kurtay | Dilara Tuğçe Özdil | Züleyha Yılmaz

Yayıncı: Ankara University

Ana Başlıklar: Farmasotik Kimya

Dergi: Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.48 Issue 1, pp.56-74

Belge Tipi: Makale

Yayın Tarihi: 1/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001300945

pISSN: 1015-3918

Sayı

Yazarlar:

Harun Nalçakan | Gülbin Kurtay | Dilara Tuğçe Özdil | Züleyha Yılmaz

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.48 Issue 1, pp.56-74

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001300945

pISSN:

1015-3918