Synthesis and anti-HIV-1 activity evaluation of Keggin-type polyoxometalates with amino acid as organic cations

Abstract

Polyoxometalates (POMs), as a class of multinuclear metal oxygen clusters, have promising biological activities. And their amino acid derivatives will lead to better pharmacological activity by the diversity in structures and properties. With reference to the anti-HIV-1 activities of PM-19 (K₇PTi₂W₁₀O₄₀) and its pyridinium derivatives, a series of novel Keggin-type POMs with amino acid as organic cations (A₇PTi₂W₁₀O₄₀) were synthesized by hydrothermal synthetic method. The final products were characterized by ¹H NMR, Elemental analyzes and single crystal X-ray diffraction. All the synthesized compounds were obtained in the yields of 44.3-61.7% and evaluated the cytotoxicity and anti-HIV-1 activity in vitro. Compared with the reference compound PM-19, the target compounds had a lower toxicity to TZM-bl cells and a higher inhibitory activity against HIV-1. Among them, compound A3 showed higher anti-HIV-1 activity with IC₅₀ of 0.11 nM than that of PM-19 with 4.68 nM. This study demonstrated that combination of Keggin-type POMs and amino acids can be a new strategy to enhance the anti-HIV-1 biological activity of POMs. All results will be expected to helpful for developing more potent and effective HIV-1 inhibitors.

Keywords: Amino acids; Anti-HIV-1; Biological activity; Polyoxometalates; Synthesis.