Recognition of specific nucleic acid sequences using small molecules is the subject of a large number of studies. Interest in such research stems from the fact that gene expression in all living organisms is controlled by regulatory proteins that bind to specific sequences on single- or double-stranded nucleic acids. In addition to anticancer therapies, small molecules that emit specific or at least highly selective signals after binding to specific DNA and RNA sequences are important for many technologies used in molecular biology and medicine.
In recent years, in the discovery of new drugs, there has been a renewed interest in natural bioactive compounds or bioactive compounds synthesized on the basis of the leading (eng.hit) structure of a natural compound. Some of these compounds refer to a structurally very diverse group, lignans and related structures. The best-known among them is podophyllotoxin, the optimization of which resulted in the antitumor drugs etoposide, etopofos and teniposide.
Considering the low occurrence in nature (only five natural benzoxanthene lignans are known so far), but also the small utilization obtained during the few attempts to synthesize derivatives, the biological properties and possible pharmacological applications of benzoxanthene lignans are almost unexplored.
The goals of the proposed project are:
1) to characterize in detail the binding interaction of lignan derivatives with DNA and RNA targets in the bioanalytical system and to determine the influence of the properties of extensions on C1 and C2 atoms of the benzoxanthene ring on binding to double-stranded and single-stranded DNA and RNA
2) choose a compound or compounds that will specifically/selectively (e.g. high binding affinity or specific spectroscopic response) recognize the secondary conformation and/or sequence of the polynucleotide
3) investigate the possible connection between the binding potential of selected compounds and antiproliferative activity in cell culture (in vitro system)
4) educate a young researcher (graduate student)
5) publish the work in a journal cited in the Wos database of rank Q1.