Synthesis and Cytotoxic Mechanism of Sulfated Alkyl Oligosaccharides Having Potent Anti-HIV Activity

Abstract

Three sulfated 1-alkyl-triazole-maltoheptaosides bearing long-chain alkyl groups (C6, C12, and C18) at the reducing ends were synthesized and subjected to surface plasmon resonance with liposomes to elucidate the cytotoxic mechanism of sulfated alkyl oligosaccharides having potent anti-HIV activity. With increasing the length of the alkyl groups, the cytotoxicity of nonsulfated and sulfated 1-alkyl-triazole-maltoheptaosides against MT-4 cells increased to CC₅₀ values of 102 and 72 μg/mL from a low cytotoxicity of CC₅₀>1000 μg/mL. Nonsulfated and sulfated 1-alkyl-triazole-maltoheptaosides bearing a C18 alkyl chain showed the highest apparent association-rate constant (k_a=1.20×10⁵ and 1.00×10⁷ 1/M, respectively) and lowest dissociation-rate constant (k_d=7.30×10^‒7 and 1.39×10^‒4 1/s, respectively) constants with the liposomes, indicating that the alkyl groups bearing longer-chains interact tightly with the liposomes. The results suggest that the longer-chain alkyl groups penetrate into the lipid bilayer of MT-4 cells to induce cytotoxicity. Considering the proposed cytotoxic mechanism, the antibacterial activity of the 1-alkyl-triazole-maltoheptaosides against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis was preliminarily investigated, finding certain antibacterial activity.