Synthesis of Novel Arsonolipids and Development of Novel Arsonoliposome Types

Abstract

Arsonolipids represent a class of arsenic-containing compounds with interesting biological properties either as monomers or as nanostructure forming components, such as arsonoliposomes that possess selective anticancer activity as proven by in vitro and in vivo studies. In this work, we describe, for the first time, the synthesis of novel arsono-containing lipids where the alkyl groups are connected through stable ether bonds. It is expected that this class of arsonolipids, compared with the corresponding ester linked, will have higher chemical stability. To accomplish this task, a new methodology of general application was developed, where a small arsono compound, 2-hydroxyethylarsonic acid, when protected with thiophenol, can be used in an efficient and simple way as a building block for the synthesis of arsono-containing lipids as well as other arsono-containing biomolecules. Thus, besides the above-mentioned arsonolipid, an arsono cholesterol derivative was also obtained. Both ether arsonolipid and arsono cholesterol were able to form liposomes having similar physicochemical properties and integrity to conventional arsonoliposomes. Furthermore, a preliminary in vitro anticancer potential assessment of the novel ether arsonolipid containing liposomes against human prostate cancer (PC-3) and Lewis lung carcinoma (LLC) cells showed significant activity (dose- and time-dependent), which was similar to that of the conventional arsonoliposomes (studied before). Given the fact that novel arsonolipids may be more stable compared to the ones used in conventional arsonoliposomes, the current results justify further exploitation of the novel compounds by in vitro and in vivo studies.