Semisynthetic teicoplanin derivatives as new influenza virus binding inhibitors: Synthesis and antiviral studies

Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents

“…Although the antiviral mode of action of 1a and 1b remains to be elucidated, we observed that these dually octylated teicoplanin pseudoaglycon derivatives inhibit influenza virus-induced hemagglutination, suggesting that they interfere with the binding interaction between the viral HA and sialylated host cell receptors. We also found that the lipophilic side chains in these molecules are essential for antiinfluenza virus activity, since changing these octyl chains to methyl groups (1c) completely abolished the antiviral effect [20]. Unfortunately, the strong activity of 1a and 1b was accompanied by high cytotoxicity, while the inactive and less amphiphilic 1c was only moderately toxic.…”

“…Next, we found that a special lipophilic modification of teicoplanin pseudoaglycon also resulted in derivatives with high antiinfluenza virus activity [20]. These derivatives contain a sugar unit carrying two n-octyl chains, and this lipophilic auxiliary is attached to teicoplanin pseudoaglycon through a tetraethylene glycol chain and a triazole ring (1a and 1b, Fig.…”

“…Structure of previously synthesized teicoplanin derivatives. Compounds 1a, 1b, 2a and 2d showed promising anti-influenza virus activity; 1c, 2b, and 2c were inactive; and 2e showed modest activity [20,21]…”

Teicoplanin inhibits Ebola pseudovirus infection in cell culture

“…This observation together with the results of pre-and post-attachment assays suggest that the mechanism of inhibition of pEBOV by teicoplanin is by blocking virus entry. Teicoplanin and its derivatives have been reported to inhibit several viruses such as HIV (Balzarini et al, 2003;Preobrazhenskaya and Olsufyeva, 2006), influenza (Bereczki et al, 2014), HCV (Maieron and Kerschner, 2012;Obeid et al, 2011), dengue virus and other flaviviruses (De Burghgraeve et al, 2012), and coronaviruses including SARS-CoV and FIPV (Balzarini et al, 2006). Because all of these viruses are enveloped viruses, we questioned whether teicoplanin inhibits a wide variety of enveloped viruses but not nonenveloped viruses.…”

Synthesis and antibacterial evaluation of some teicoplanin pseudoaglycon derivatives containing alkyl- and arylthiosubstituted maleimides

“…Applying various approaches including squaric acid conjugation method, azide-alkyne cycloaddition reaction or three-component isoindole formation, we have prepared a large set of new derivatives exhibiting high antibacterial [10][11][12][13] and, in some cases, robust antiinfluenza virus activity. [14][15][16][17] Recently, Caddick, Baker and coworkers [18][19][20][21] reported on applications of 3,4-dibromomaleimides for site-specific protein modification and bioconjugation. The method is based on addition-elimination reaction of thiols to the bromomaleimides leading to regeneration of the double bond resulting in thiomaleimide products (Scheme 1).…”