Azaheterocycles. the searching of highly active molecules as potential drug candidates

Work number - M 17 AWARDED

Presented Danylo Halytsky Lviv National Medical University

Authors:
1. KONECHNYI Yulian – PhD, associate professor of Department of Microbiology Danylo Halytsky Lviv National Medical University
2. YUSHYN IHOR – PhD, assistant professor of Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University
3. POLOVKOVYCH Sviatoslav – DSc, associate professor, professor of Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology Lviv Polytechnic National University

Within the framework of various synthetic approaches, several previously unknown hybrid molecules based on five-membered heterocycles, as well as a series of new condensed and exo-functionalized azaheterocyclic derivatives, were synthesized. For this purpose, highly efficient reactions of [2+3]-cyclocondensation, azo coupling, hydrolysis, aminolysis, nucleophilic substitution, alkylation, acylation, Knoevenagel, Claisen-Schmidt, hetero-Diels-Alder, [3+2]-cycloaddition and Pd-catalyzed Buchwald-Hartwig reaction were used. The structure and purity of the synthesized compounds were confirmed by ¹H and ¹³C NMR spectroscopy, X-ray structural analysis, and mass spectrometry. Based on the screening studies of the biological activities of synthesized azaheterocycles, several promising agents with antitumor activity were detected, also using phenotypic screening and modern in silico approaches revealed "hit compounds" with antimicrobial, antifungal and anti-inflammatory effects, which indicates the prospects of this class of compounds in the search for new potential drugs. In addition, highly active compounds with the best cytotoxic effect on human Jurkat T-leukemia cell lines were identified. Some of the resulting products were found to be potential PAPR1/2 inhibitors and apoptosis inducers, interacting with PAPR in a novel mechanism that is not characteristic of other PARP inhibitors. 

Number of publications: individual monographs (textbooks, manuals), collective monographs (textbooks, manuals), incl. - in foreign publications, 36 articles in magazines included in category "A" (including 27 in foreign publications) and 2 articles in magazines included in category "B", - theses of reports. The total number of references to authors' publications/h-index by work according to databases is, respectively: Web of Science 121/7, Scopus 174/8, Google Scholar 239/10. Received - patents for inventions of Ukraine and - other countries, 2 patents for a utility model, an industrial design (for social and humanitarian sciences, certificates of copyright registration for a work) or other received protective documents for objects of intellectual property law.

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