New Design Compounds for Bone Cancer Treatment: Broader Bioactivity of Silicon Modified Methotrexate

Complex diseases such as cancer are mostly described by combining negative effects of multiple biological factors or pathways. Based on that, multi-targeted approach for treating cancer is gaining interest. The aim of this study is to introduce a computational approach and to design new, multi-targeted drug candidates for treatment of bone cancer. In this approach, the FDA approved drugs of bone cancer were evaluated in terms of their molecular pharmaceutical properties and their bioactivity parameters predicted by bioinformatics and cheminformatics softwares. Among them, Methotrexate was chosen as a lead molecule due to its broader spectrum of bioactivity on the most important drug targets reported in literature. The lead molecule was exposed to basic bioisosteric modifications to obtain a better drug compound with improved bioactivity and a stronger drug-likeness profile using the known drug structure. Design compounds produced by a number of bioisosteric modifications performed on the 2D structure of the lead compound were evaluated in terms of both criteria; bioactivity and drug-likeness. Silicone modified compounds M4, M13, M14, and M15 showed a much broader spectrum of biological activity than that of the approved compound Methotrexate. The interesting effect of silicone incorporation makes our compounds promising drug candidates for further pharmaceutical investigation.

Anahtar Kelimeler:

in silico, computer aided drug design, bone cancer, ADME, bioactivity, drug-likeness

New Design Compounds for Bone Cancer Treatment: Broader Bioactivity of Silicon Modified Methotrexate

Keywords:

in silico, computer aided drug design, bone cancer, ADME, bioactivity, drug-likeness in silico, computer aided drug design, bone cancer, ADME, bioactivity, drug-likeness,

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