Evaluation of DNase I inhibitory activity on synthetic halogenated chalcone derivatives

Abstract

Chalcones represent a class of bioactive, naturally occurring compounds, consisting of two aromatic rings (ring A and ring B) linked by α,β-unsaturated three-carbon chain (Table 1). In nature, chalcones are abundant in fruits, vegetables and various plants, many of which have found their place in traditional herbal medicine for the therapy of various medical conditions (Orlikova et al., 2011). Chalcone derivatives, either from natural sources or synthetically obtained, have demonstrated numerous bioactivities, and are considered as privileged scaffolds in medicinal chemistry. It has been shown that this group of compounds exerts antioxidant, antineoplastic, antiangiogenic, hypolipidemic, antimicrobial, antiinflammatory, tyrosine inhibitory, vasorelaxant and other activities. Chalcones have also been reported to possess enzyme inhibitory activities towards numerous pharmacologically significant enzymes including cholinesterases, xanthine oxidase, cyclooxygenase, lipoxygenase, etc. (Zhuang et al., 2017). Deoxyribonuclease I (DNase I) is one of the most important enzymes in the human body which catalyzes DNA hydrolysis forming 5'-oligonucleotides. This enzyme is one of the main nucleases responsible for DNA fragmentation during programmed cell death (apoptosis) (Oliveri et al., 2001; Samejima and Earnshaw, 2005). Elevated levels of DNase I can lead to increased DNA fragmentation and excessive cell death, thus contributing to the development of numerous pathological conditions (cardiovascular, autoimmune, neurodegenerative) (Oliveri et al., 2001). Having in mind the pathophysiological importance of DNase I, the relatively small number of known organic inhibitors of this enzyme, as well as the fact that there is no inhibitor defined as a "gold standard", there is a need for finding new efficient DNase I inhibitors. To the best of our knowledge, there is no information of chalcones as DNase I inhibitors, therefore this experiment represents an entry into an unexplored field which will hopefully result in increased interest for further research on this topic and discovery of new active chalcone structures.