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Analysis of Methylene-bisphosphonic Acids by in silico and in vitro Methods
* 1 , 1 , 1 , 2
1  D.K. Zabolotny Institute of Microbiology and Virology NAS of Ukraine, Kyiv, Ukraine
2  Institute of Organic Chemistry NAS of Ukraine

Published: 01 November 2017 by MDPI in 3rd International Electronic Conference on Medicinal Chemistry session ECMC-3

On a global scale, Epstein-Barr virus (EBV) infects over 90% of the adult population and is responsible for ~1% of all human cancers. Fluorine is one of the most abundant elements on earth. However, it occurs extremely rarely in biological compounds. The introduction of the fluorine atom(s) into many biologically active molecules can bring about remarkable and profound changes in their properties. Development of potential drugs is closely related to in silico methods, which include PASS, QSAR, COMPARE-analysis and more. 

The aim of this work was to analyze the potential biological activity and the target of action of derivatives of bisphosphonic acids by using in silico methods and examined received results by in vitro study. For this purpose, PASS software, web-server PharmMapper, PCR, MTT assay, trypan blue and neutral red assay were used.

According to PASS prediction two compounds (10s-20 and 10s-21) may possess antiviral activity, Pa/ Pi was 0,294/0,005 and 0,214/0,084, respectively. Also, all compounds may possess a cytochrome c as substrate. Several targets were identified by using molecular docking (PharmMapper). It was shown that a lot of possible targets are proteins, such as Gag-Pol protein (viral protein) and different kinds of protein kinases. A study in vitro shown anti-EBV activity for all compounds. On the other hand, derivatives of bisphosphonic acids had a high level of cytotoxicity on different lymphoblastoid cell lines.

Therefore, the in silico screening presents a good approach for the development of new anti-EBV agents. Our results showed, that derivatives of bisphosphonic acids may possess  apoptosis modulating properties for treatment of lymphoproliferative diseases.

Keywords: Epstein-Barr virus, fluorinated bisphosphonic acids, PASS