Synthesis and Characterization of Long-Chain Tartaric Acid Diamides as Novel Ceramide-Like Compounds

Abstract

Ceramides play a crucial role in the barrier function of the skin as well as in transmembrane signaling. In this study long aliphatic chain tartaric acid diamides able to replace ceramides in an in vitro model of the stratum corneum lipid matrix due to their similar physico-chemical properties were synthesized from diacetoxysuccinic anhydride in four steps. Their pro-apoptotic effect on fibroblast cells was also investigated.

A new tool to assess ceramide bioactivity: 6-bromo-7-hydroxycoumarinyl-caged ceramide

“…3 To supplement the in situ ceramide level, investigators have focused on exogenous addition of natural ceramide; unfortunately, as long-chain ceramide is not membrane permeable, the delivery employs a widely used ethanol/dodecane mixture. 4 However, dodecane alters membrane permeability, 5 and as little as 1 M dodecane induces membrane defects and nonspecific activation of cell signaling pathways. 6 Alternatively, water-soluble, short-chain ceramides have been used as mimics of their long-chain natural counterparts, especially to trigger apoptosis or inhibit signaling in human cancer cells by ceramide accumulation.…”

Preparation, Physicochemical Properties, and Transfection Activities of Tartaric Acid-Based Cationic Lipids as Effective Nonviral Gene Delivery Vectors

“…40) Tartaric acid, a multi-functional molecule, has two hydroxyl and two carboxyl groups as reactive sites, which is suitable as the backbone in the design of cationic lipids through easily modified with different head group and alkyl hydrophobic tail.…”

Methods to Evaluate Skin Penetration In Vitro

“…Compared to the OECD recommendation, this is still one order of magnitude higher, but it is closer to the concept of finite dose [65]. Skin-PAMPA membrane was produced by using cholesterol, free fatty acid, and a ceramide-analogue compound that imitates the features of lipid matrix [66]. The donor plate of the conventional skin-PAMPA procedure requires the use of a large amount of sample, which does not meet the concept of finite dose.…”

“…Widely used methods are the measurement of tritium water permeability, the measurement of transepidermal water loss, and the determination of transepidermal electrical resistance. A relatively new method is the use of the tritium-labeled internal reference standard, where integrity testing is performed simultaneously with the measurement [60][61][62][63][64]66,67]. For each method, it can be stated that the measurements are different and not properly regulated.…”