BENZOFENON-3’ÜN GELİŞİMSEL VE METABOLİK YOLAKLARA ODAKLANAN İN SİLİKO TOKSİSİTE PROFİLLEMESİ

Öz

Amaç: Bu çalışma, kişisel bakım ürünlerinde yaygın olarak kullanılan bir ultraviyole (UV) filtresi olan Benzofenon-3’ün (BP-3) gelişimsel toksisite potansiyelini in siliko analizler kullanarak değerlendirmeyi amaçlamaktadır.

Gereç ve Yöntem: Benzofenon-3’ün toksikolojik özellikleri ProTox ve deTOX platformları kullanılarak tahmin edilmiştir. Gelişimsel toksisite değerlendirmesi gebeliğin birinci, ikinci ve üçüncü trimester dönemleri için modellenmiştir. Ayrıca BP-3’ün insan sitokrom P450 enzimleri (CYP1A2, CYP2C19, CYP2D6) ile potansiyel etkileşimleri moleküler kenetlenme analizleri ile araştırılmıştır.

Sonuç ve Tartışma: Literatür verileri, BP-3’ün plasental bariyeri aşarak sistemik dolaşıma geçebildiğini göstermektedir. In siliko analiz sonuçları, özellikle gebeliğin ikinci trimesterinde yüksek gelişimsel toksisite potansiyelini (olasılık: 0.952) ortaya koymuştur. Moleküler kenetlenme analizleri BP-3’ün CYP1A2’ye güçlü bağlanma afinitesi sergilediğini ve CYP2C19 ile CYP2D6 enzimleri ile anlamlı etkileşimler oluşturduğunu göstermiştir. Toksisite katkı haritalaması ise toksisite ile ilişkili spesifik moleküler bölgeleri desteklemiştir.

Anahtar Kelimeler

• Benzofenon-3
• gelişimsel toksisite
• in siliko analiz
• ProTox
• sitokrom P450

Etik Beyan

Bu çalışma yalnızca bilgisayar destekli (in silico) analizler içermektedir, insan veya hayvan denekleri üzerinde herhangi bir deneysel uygulama yapılmamıştır. Bu nedenle etik kurul onayı gerekmemektedir.

IN SILICO TOXICITY PROFILING OF BENZOPHENONE-3 WITH FOCUS ON DEVELOPMENTAL AND METABOLIC PATHWAYS

Öz

Objective: This study aims to evaluate the developmental toxicity potential of Benzophenone-3 (BP-3), a widely used ultraviolet (UV) filter in personal care products, through in silico analyses.

Material and Method: The toxicological properties of BP-3 were predicted using the ProTox and deTOX platforms. Developmental toxicity was modeled specifically for the first, second, and third trimesters of pregnancy. Additionally, the potential interactions of BP-3 with human cytochrome P450 enzymes (CYP1A2, CYP2C19, CYP2D6) were investigated via molecular docking analyses.

Result and Discussion: Literature data confirm that BP-3 can cross the placental barrier and enter systemic circulation. In silico predictions indicated a high developmental toxicity potential, particularly during the second trimester (probability: 0.952). Molecular docking analyses revealed strong binding affinity of BP-3 to CYP1A2, as well as notable interactions with CYP2C19 and CYP2D6, suggesting possible interference with drug metabolism and endocrine regulation. The findings were further supported by structural toxicity contribution mapping, highlighting specific molecular regions responsible for toxicity.

Anahtar Kelimeler

• Benzophenone-3
• cytochrome P450
• developmental toxicity
• in silico analysis
• ProTox

Etik Beyan

This study is based solely on computer-aided (in silico) analyses and does not involve any experiments on human or animal subjects. Therefore, ethical committee approval was not required.

Kaynakça

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