Development of a Water Soluble Self-assembling Analogue of Vizantin

Abstract

Vizantin, 6,6′-bis-O-(3-nonyldodecanoyl)-α,α′-trehalose, has been developed as a safe immunostimulator on the basis of a structure-activity relationship study with trehalose 6,6′-dicorynomycolate. Our recent study indicated that vizantin acts as an effective Toll-like receptor-4 (TLR4) partial agonist to reduce the lethality of an immune shock caused by lipopolysaccharide (LPS). However, because vizantin has low solubility in water, the aqueous solution used in in vivo assay systems settles out in tens of minutes. Here, vizantin was chemically modified in an attempt to facilitate the preparation of an aqueous solution of the drug. This paper describes the concise synthesis of a water-soluble vizantin analogue in which all the hydroxyl groups of the sugar unit were replaced by sulfates. The vizantin derivative displayed micelle-forming ability in water and potent TLR-4 partial agonist activity.

Maintenance of homeostasis by TLR4 ligands

“…Vizantin is a trehalose diester consisting of two achiral β-branched fatty acids, 2-nonylundecanoic acid, fused to the hydroxyl groups at the 6, 6’ positions of trehalose. Additionally, researchers successfully created sulfated Vizantin by sulfating the hydroxyl group of the trehalose moiety, making it water-soluble ( 90 ) ( Figure 1 ).…”