Multi-targeted anti-leukemic drug design with the incorporation of silicon into Nelarabine: How silicon increases bioactivity
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Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
ELSEVIER
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Acute Lymphoblastic Leukemia (ALL) represents 30% of all childhood cancers and children younger than 5 years old have the highest risk for developing ALL. Existing ALL drugs do not respond in approximately 20% of treatment. Therefore, drug development studies against ALL must be continued with either developing existing drugs or discovering new ones. In this study, we evaluated the U.S Food and Drug Administration (FDA) approved ALL drugs according to their physicochemical and pharmaceutical properties, and Nelarabine was found to have the highest bioactivity score. Using the key strategy of bioisosterism commonly accepted by medicinal chemists, we investigated in silico ADME properties, drug-likeness, and biological activity of new designed twenty-four compounds including Nelarabine. The results were evaluated in terms of two classifications: broad spectrum biological activity and filtering of five different drug likeness criteria of the literature including Lipinski's rule of five. We interestingly observed that silicon incorporated compounds exhibited better performance on both criteria by targeting broader spectrum of drug receptors including G-protein coupled receptor (GPCR), ion channel modulator, kinase inhibitor, protease and enzyme inhibitor and by satisfying all of five different drug-likeness criteria reported in the literature. Design compound C19 appeared as a potential drug candidate for further pharmacological research.
Açıklama
Anahtar Kelimeler
Pharmacokinetic, ADME, In silico, Anti-leukemia, Silicon, Drug-likeness
Kaynak
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
134
Sayı
Künye
Eryilmaz, E. (2019). Multi-Targeted Anti-Leukemic Drug Design With The İncorporation Of Silicon İnto Nelarabine: How Silicon İncreases Bioactivity. European Journal Of Pharmaceutical Sciences, 134, 266-273.
