Despite the development of many agents, we still do not have an agent that would destroy HIV-1 virus in a body. Active ingredients that prevent the propagation of HIV-1 and contribute to the reduction of disease rate and mortality of infected people are being used. DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-grabbing Non-integrin) is a C-type lectin from group II. It is specifically expressed on dendritic cells, which are the most powerful antigen presenting cells; their key role is to regulate immune response. Dendritic cells express a number of receptors on their surface, which are able to recognize different bacterial and viral pathogens. Among these receptors, the C-type receptors need to be mentioned, through which HIV-1 can enter the host cell. DC-SIGN recognizes HIV-1 and enables its entry into a host cell without activating the host immune system. This is how HIV-1 avoids normal lytic degradation and deludes the immune response. A similar mechanism was observed in many other pathogenic organisms, so it seems reasonable to prevent the interaction between the pathogen and DC-SIGN. Antagonists of receptor DC-SIGN are therefore potential antiviral and antibacterial agents, which could prevent infection with different pathogens (e.g. HIV, Mycobacterium tuberculosis) in its early stages. FimH receptor is also placed among lectin receptors. It can be found on type I fimbriae that cover the surface of bacteria and allow them (e.g. Escherichia coli) to attach to specific receptors located on the membrane of epithelial host cells. Anti-adhesive therapy with FimH antagonist may be particularly effective against the bacteria that have already developed resistance to antibacterial agents. In this dissertation we synthesized a focused library of diarylglycerolomanosides as new potential antagonists of DC-SIGN and FimH. The most important structural element of the designed compounds is a D-mannose moiety, which forms coordinative bonds with Ca2+ and additional hydrogen bonds with amino acid residues in the binding site. With a variety of aryl substituents on the glycerol spacer, we wanted to ensure additional hydrophobic and/or π-π interactions with the side chain of Phe313 in DC-SIGN CRD. The synthesized compounds were tested for their activity on DC-SIGN receptor as well as FimH due to their similarity to the known FimH antagonists. Despite the fact that the original idea was the design and synthesis of DC-SIGN antagonists, synthesized compounds show better activity on the FimH receptor.
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