6- AND 7-AMINOMETHYL-11H-INDENO[1,2-b]QUINOXALINE-11-ONES – SYNTHESIS, DNA AFINITY AND TOXICITY

Abstract

The actuality of the antivirals design and synthesis capable to the reproduction inhibition of emerging and mutated viruses is now especially evident against the background of the SARSCoV-2 outbreak in the world. New 6- and 7-aminomethyl-11H-indeno[2,3-b]quinoxalin-11-ones (AMIQ) were synthesized to obtain new DNA intercalators with the expected antiviral activity caused of their ability to intercalate DNA. The synthesis was performed by condensation of ninhydrin with 2,3- and 3,4-diaminotoluenes, followed by N-bromosuccinimide bromination and amino-debromination by the action of an excess of secondary amines on the corresponding bromomethyl derivatives. The structures of the synthesized compounds were confirmed by mass spectrometry and IR-spectroscopy. The molecular ion peaks present at the mass spectra of all compounds, m/z values of fragmentation ions correspond to the trivial fragmentation rote; absorption bands in the IR spectra correspond to the presented functional groups. All synthesized AMIQ demonstrate the ability to compete with ethidium bromide for DNA binding sites, which is typical for DNA intercalators. The AMIQ affinity to DNA was investigated by this method and appeared as close to that of amixine (lgKa =5.7 – 6.8). The amino groups’ structure and the position of the substituent do not significantly affect the affinity at P < 0.05. AMIQ toxicity was evaluated in a 24-hour toxicity test against A. parthenogenetica , in which these compounds were less toxic than amixine in most cases with –lgLC50 values less than 4. Obtained results testify to perspectivity of the further AMIQ and their analogs investiagations as potential broad spectra antiviral agents.