Development of potential HIV-1 inhibitors by in silico click chemistry and molecular modeling methods

Design of novel potential HIV-1 inhibitors able to block CD4-binding site of the envelope gp120 protein was carried out based on click chemistry in silico, a methodology allowing one to generate a large number of drug candidates by assembly from small modular units and to study their properties. Using the methods of molecular modeling, the neutralizing activity of designed molecules was evaluated, as a result of which five leading compounds that are promising for synthesis and biological trials were identified. Their chemical formulas are C$_{24}$H$_{23}$N$_7$O$_2$, C$_{23}$H$_{20}$N$_6$O$_2$, C$_{21}$H$_{17}$F$_{3}$N$_6$, C$_{22}$H$_{20}$ClN$_9$O and C$_{19}$H$_{15}$N$_9$O. It has been shown that these compounds can be used as good scaffolds for the development of novel potent and broad anti-HIV drugs with extensive viral neutralization effect.