Computational assessment of the platinum (II) complex of imidazolidine dioximes substituted with methoxydiglycol units: from activation to DNA binding

Öz

To overcome the issue of toxicity inherent in the approved anticancer agents, many cisplatin derivatives continue to be designed and tested today. Recently, we have proposed a new series of platinum complexes with highly potent imidazolidine dioxime ligands, a combination of two active ligands targeting DNA, substituted with aliphatic carbon chains or aromatic moiety. Quantum mechanical calculations have revealed their potential activity, particularly highlighting the potentially enhanced activity of complexes with aliphatic substituents in DNA platination. Here, we extend our previous study with the inclusion of methoxydiglycol unit (2-(2-methoxyethoxy)ethyl substituents) into the imidazolidine dioxime ligands of our previously proposed complexes to possibly enhance the solubility and bioavailability. Our current investigation focuses on modeling the aquation and DNA binding reactions to assess the potential of this modification and the results are compared to cisplatin.

Anahtar Kelimeler

• Platinum drugs
• anticancer agents
• cisplatin derivatives
• density functional theory

Metoksidiglikol ile sübstitüe edilmiş imidazolidin dioksimlerinin platin (II) kompleksi üzerine hesapsal bir çalışma: aktivasyondan DNA bağlanmasına

Öz

Onaylanmış antikanser ajanlarının sahip olduğu toksisite sorunlarının üstesinden gelmek amacıyla, günümüzde birçok cisplatin türevi tasarlanmakta ve test edilmektedir. Yakın zamanda, DNA’yı hedef alan iki aktif ligand içeren, alifatik karbon zincirleri veya aromatik yapı ile sübstitüe edilmiş imidazolidin dioksim ligandlarına sahip yeni bir platin kompleks serisi önerdik. Kuantum mekanik hesaplamalar, özellikle alifatik sübstitüentlerin DNA platinasyonu üzerindeki potansiyel aktivitesini vurgulamıştır. Bu çalışmada, çözünürlük ve biyoyararlanımın artırılması amacıyla daha önce önerdiğimiz komplekslere metoksidiglikol (2-(2-metoksietoksi)etil) sübstitüenti dahil edilmiş ve bu modifikasyonun potansiyelini değerlendirmek için yeni önerilen platin kompleksinin hidroliz ve DNA bağlanma reaksiyonları hesapsal olarak çalışılmış ve sonuçlar aktif kullanımda olan cisplatin ile karşılaştırılmıştır.

Anahtar Kelimeler

• Platin ilaçları
• antikanser ajanları
• cisplatin türevleri
• yoğunluk fonksiyoneli teorisi

Kaynakça

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