HIV‑1 X4 Activities of Polycationic “Viologen” Based Dendrimers by Interaction with the Chemokine Receptor CXCR4: Study of Structure–Activity Relationship

Abstract

A series of “viologen” based dendrimers with polycationic scaffold carrying 10, 18, 26, 42, and 90 charges per molecule were used to determine the structure–activity relationship (SAR) with regard to HIV-1 inhibitory activity. The studies involved five compounds with a high activity against HIV-1 already utilized in our previous study and five new dendrimers. Such dendrimers block HIV-1 entry into the cell, indicating that they bind to HIV-1 surface proteins and/or on the host cell receptors required for entry. The increasing positive character of dendrimers leads to more cytotoxicity. The 10 charges dendrimers (<b>1</b>, <b>6</b>) have less influence on the cell viability but low inhibition of the binding of the CXCR4 mAb clone 1D9. Thus, dendrimers with 18 charges (<b>2</b>, <b>7</b>) are the most promising CXCR4 imaging probes. We report the design, synthesis, and biological activity of new HIV-1 inhibitors that are conceptually distinct from those of the existing HIV-1 inhibitors