А series of the work «Development and bio-testing of novel compounds with antiviral and antitumor activity»

Work number - M 27 AWARDED

Authors: PanchukR.R., MalyukinaM.Yu,.HavrylyukD.Ya.,IvanovaO.S., Bogorad-KobelskaO.S.

Presented for the annual awards competition of the President of Ukraine for young scientists in 2015.

The series of scientific papers consists of 95 scientific articles published during 2009-2014 years, and is dedicated to comprehensive study of a number of new compounds possessing antiviral and antitumor activity

It was demonstrated that biphenyl derivativespossess high antiviral activity, which exceeds the effectiveness of the biological effect of commercial drug "Amixin", which is widely used in clinical practice.For studying of bio-safety of novel compounds (namely, their toxicity, mutagenicity, ability to induceinterferon production) appropriate methods were applied by the authors of the study. On the basis of study of the impact of diphenyl derivatives on the changes in membrane potential of mitochondria it was found that these compounds mediate their activities due to activation of mitochondrial antiviral signaling pathway, which results in the induction of IFN type I .

Novelanticancer drugs based on 4-thiazolidonescaffold  were designed by means of molecular modeling  and synthesizedusing modern methods of organic chemistry. Based on the in vitro screening of 20 members of that group it was found that the specific structure of the side groups in the 4th positionof4-thiazolidone molecule plays crucial mechanisms in the resulting death of tumor cells. Using it was revealedthat reactive oxygen species play a crucialrole in realization of anticancer activity of novel4-thiazolidones bytriggerringmitochondria-mediatedapoptosis. For determining of this phenomenanovel assays were applied, which are based on fluorescent probes  and were developed by the authors of this work.

It was revealedthatimmobilization of anticancer drugs on the novel nanoscale carriers - C60 fullerenes, which also possess their own antioxidant activity, was accompanied not only decrease their side effects, but also enhancement of their therapeutic effects in experimental models of tumors in mice.

Concluding, the results of the proposed series of works are important for further pre-clinical studies of these compounds aiming at development of new strategies for the treatment of human malignancies and introduction into clinical practice of novel domestic advanced and efficient multifunctional nanomaterials with antiviral and antitumor activity

Results of the studies of proposed series of works are outlined in 95articles (including 29 in foreign journals), 6 patents of Ukraine and 141 abstracts of conferences. Works of authors are cited in 250 academic journals, overall citation index is 338 (according to Scopus database), h-index = 11, overall impact factor – 49. Thetotalnumberofauthors’ publicationsis239.