Hidroksi- ve Sülfonamid- Azobenzen Platin (II) Komplekslerinin Yapısal, Spektroskopik ve Anti-Kanser Özellikleri: DFT ve Moleküler Yerleştirme Çalışmaları

Yıl 2018, Cilt: 39 Sayı: 4, 1036 - 1051, 24.12.2018

Sultan Erkan

https://doi.org/10.17776/csj.421027

Cited By: 4

Öz

Bidentat ligandlar olan sülfonamid-((E)-2-(4-metilfenilsülfonamido)-2',6'-diizoazobenzen, HL1) ve
hidroksi-azo-2,6-diflorobenzen ((E)-2-((2,6-diflorofenil)diazenil)fenol, HL2)
taşıyan üç platin (II) kompleksi ([Pt(L1)(DMSO)Cl], [Pt(L2)(DMSO)Cl] ve [Pt(L2)₂])
en uygun seviye olarak belirlenen B3LYP/6-31+G(d) ve B3LYP/LANL2DZ/6-31+G(d)
seviyesi ile optimize edildi. Optimize yapılardan elde edilen yapısal
parametreler (bağ uzunluklar ve bağ açıları), IR ve ¹H, ¹³C ve ¹⁹F-NMR
kimyasal kaymaları deneysel veriler ile kıyaslandı ve sonuçlar deneysel
sonuçlar ile uyumlu olduğu görüldü. A2780 ve A2780CP70 kanser hüclerine karşı
deneysel inhibisyon etkinlikleri HOMO enerjisi (E_HOMO), LUMO enerjisi (E_LUMO),
LUMO-HOMO enerji boşluğu (DE), sertlik (h), yumuşaklık (s), elektronegativite (c) ve kimyasal potansiyel (m) gibi kuantum kimyasal parametreler ile
kıyaslandı. Aktivite yapı arasındaki ilişki incelendi ve E_LUMO
deneysel inhibisyon etkinlik sıralaması ile bire bir uyumlu bulundu.
Anti-kanser özellik gösteren ligand ve komplekslerin moleküler elektrostatik
potansiyel (MEP) haritaları incelendi ve HL1 ve HL2 ligandları ve Comp. (1)-(3)
için kanser hücrelerine bağlanma bölgeleri belirlendi. Ayrıca MEP
haritalarından elde edilen elektrostatik potansiyel (ESP) yükleri ile ligandlar
ve komplekslerin kanser hücresine bağlanma kolaylıklarına göre sıralamaları
yapıldı. Elde edilen sıralama deneysel inhibisyon etkinlik sıralaması uyumlu
bulundu. Çalışılan ligand ve kompleksler için Hex.8.0.0 programı ile moleküler
yerleştirme çalışmaları yapıldı. A2780 ve A2780CP70 hücre çizgisine karşılık
gelen hedef proteinler (PDB ID:4M5W ve 5FI4, sırasıyla)  literatürde seçildi. 4M5W ve 5FI4 hedef
proteinleri ile HL1 ve HL2 ligandaların etkileşim enerjileri sırasıyla -300.02,
-240.80 ve -336.64, -247.04 kJ/mol olarak hesaplandı. Kompleksler ile 4M5W ve
5FI4 hedef proteinleri arasındaki bağlanma enerjileri -387.52, -285.44,
-364.88 ve -399.63, -297.8, -385.323 kJ/mol olarak hesaplandı. Bu sonuçlara göre
deneysel ve hesaplanan inhibisyon etkinlik sıralaması uyumlu bulundu. 

Anahtar Kelimeler

Platinum (II) kompleksleri, DFT ve Moleküler Yerleştirme Çalışmaları

Structural, Spectroscopic and Anti-cancer Properties of Hydroxy- and Sulfonamide-Azobenzene Platinum (II) Complexes: DFT and Molecular Docking Studies

Öz

The three platinum (II) complexes ([Pt(L1)(DMSO)Cl], [Pt(L2)(DMSO)Cl]
and [Pt(L2)₂]) bearing the bidentate ligands
sulphonamide-((E)-2-(4-methylphenylsulfonamido)-2′,6′-difluoroazobenzene,
HL1)  and hydroxy-azo-2,6-difluorobenzene
((E)-2-((2,6-difluorophenyl)diazenyl)phenol, HL2) were optimized with the optimum
levels of B3LYP/6-31+G(d) and B3LYP/LANL2DZ/6-31+G(d) level. The structural
parameters (bond lengths and ligand angles), IR and ¹H, ¹³C and ¹⁹F-NMR
spectra obtained from the optimized structures were compared with the
experimental data and the results were found to be consistent with the
experimental results. Experimental inhibition activities against A2780 and
A2780CP70 cancer cells were compared with quantum chemical parameters such as
HOMO energy (E_HOMO), LUMO energy (E_LUMO), LUMO-HOMO
energy vacancy (DE), hardness (h), softness (s), electronegativity (c) and chemical potential
(m). The relationship
between the molecular structure with the biological activity was examined and E_LUMO
order was found to be compatible with the experimental inhibition efficiency
ranking. Molecular electrostatic potential (MEP) maps were studied of ligands
and complexes exhibiting anti-cancer properties and for ligands and complexes,
regions of attachment to cancer cells were determined. In addition,
electrostatic potential (ESP) charges obtained from MEP maps of ligands and
complexes were ranked according to their ease of binding to the cancer cell.
The obtained ranking was found to be in accordance with the experimental
inhibition efficiency order. For studied ligands and complexes, molecular
docking studies were carried out with the Hex.8.0.0 program. The target
proteins (PDB ID: 4M5W and 5FI4, respectively) corresponding to the A2780 and
A2780CP70 cell lines were selected in the literature. The interaction energies
of 4M5W and 5FI4 target proteins with HL1 and HL2 ligands were calculated to be
-300.02, -240.80 and -336.64, -247.04 kJ/mol, respectively. The binding
energies between the complexes and 4M5W and 5FI4 target proteins were
calculated to be -387.52, -285.44, -364.88 and -399.63, -297.8, -385.323
kJ/mol. According to these results, the experimental and calculated inhibition
efficiency order was found to be compatible.

Anahtar Kelimeler

Platinum (II) complexes, DFT and Molecular Docking Studies

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