PARTİSYON KATSAYISI (LOG P) TAHMİNİNDE KULLANILAN YAZILIMLARIN KARŞILAŞTIRILMASI

Yıl 2019, Cilt: 43 Sayı: 1, 1 - 19, 31.01.2019

Mehmet Murat Kışla , İlkay Yildiz

Öz

        Amaç: Sentezlenecek
ilaç etken maddesi adayı bileşiklerin vücut dokularına ulaşabilmesi ve
ulaştığında da toksik etki göstermemesi gerekmektedir. Kantitatif yapı-etki
ilişkilerinin fizikokimyasal parametreler başlığında yer alan partisyon
katsayısı (log P), ilacın farmakokinetik özelliklerini etkilemektedir.
Araştırmacılar, ilaç geliştirme çalışmalarında zaman ve maliyetten tasarruf
sağlamak amacıyla log P tahmin eden yazılımlara başvurabilmektedir. Fakat bu
yazılımların tamamen doğru sonuç vermediği unutulmamalıdır. Bu çalışmada,
kullanılmakta olan bu yazılımların güvenilirliği test edilmiştir. Bunlardan
güvenilirliği onaylanan yazılım araştırmacılara partisyon katsayısının deneysel
tayininden önce fikir verebilecektir.

       
Gereç ve Yöntem: 94
bileşikten oluşan bileşik verisetinde, literatürdeki log P değerleri ile
ACD/iLab 2.0, ALOGPS 2.1 ve Molinspiration log P yazılımları aracılığıyla
hesaplanan değerler karşılaştırılmış; sapma değerlerine göre bu üç yazılımdan
en güvenilir olan seçilmiştir. Bileşiklerin partisyon katsayısı hesaplanırken
SMILES kodları kullanılmıştır.

        Sonuç ve Tartışma: 94 literatür bileşiğinden elde edilen hesaplama sonuçlarına göre
partisyon katsayısı (log P) hesaplamada en güvenilir yazılımın, en düşük
ortalama sapmaya sahip olan Molinspiration log P olduğuna karar verilmiştir. Bu
yazılımın kullanılmasıyla araştırmacılar, sentezlenen bileşiklerin partisyon
katsayısı hakkında yorum yürütebilecek olup, zaman ve maliyetten tasarruf
edebileceklerdir.

Anahtar Kelimeler

ADME/Tox, Farmakokinetik, İlaç Geliştirme, Lipofiliklik, Log P

COMPARISON OF PARTITION COEFFICIENT (LOG P) PREDICTION SOFTWARES

Öz

        Objective: Drug candidate compounds that are going to be
synthesized have to reach body tissues and show minimum toxic effects within
the body. Partition coefficient (log P), which is a physicochemical parameter
of Quantitative Structure- Activity Relationship subject, effects the
pharmacokinetical characteristic of the compound. In this context, researchers
tend to use log P prediction softwares to save both time and resources in their
drug development studies. Although, these softwares do not give a true value.
In this study, softwares that have being used were tested. The one that gets
approved for its accuracy can give some clues on the value of partition
coefficient, before determining it experimentally.

        Material and Method: In the following dataset, which
comprises of 94 compounds, logP values from literature and values that have
been calculated with softwares such as ACD/iLab 2.0, ALOGPS 2.1 ve
Molinspiration have been compared. By calculating the deviations, most reliable
of these three has been selected. SMILES notations of the compounds has been
used as an input for the calculation.

        Result and Discussion: According to the calculation results of 94 compounds, Molinspiration log
P, which has the lowest average deviation value, was selected as most reliable
log P prediction software. By using this software, scholars can comment on
partition coefficients of their synthesized compounds. Therefore, hopefully
they can save both time and resources.

Anahtar Kelimeler

ADME/Tox, Drug Development, Lipophilicity, Log P, Pharmacokinetics

Kaynakça

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