Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

Abstract

The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59–87%) and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts). The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2.

Synthesis, Characterization, and In Vitro Cancer Cell Growth Inhibition Evaluation of Novel Phosphatidylcholines with Anisic and Veratric Acids

“…Anisic acid (ANISA) ( 1a ) and veratric acid (VERA) ( 1b ) were purchased from Sigma-Aldrich Chemical Co (St. Louis, MO, USA). sn -Glycero-3-phosphocholine (GPC) in the enantiomerically pure form was purchased from Bachem and converted to the cadmium chloride complex (GPC × CdCl 2 ) using described earlier method [ 16 ]. Phospholipase A 2 (Lecitase 10L; 10,000 LEU/mL) was a gift from Novozymes (Bagsvaered, Denmark).…”

“…The GPC × CdCl 2 complex ( 2 ) was prepared according to the procedure described before [ 16 ]. In the next step, cadmium complex of GPC was acetylated with methoxybenzoic acids in positions sn -1 and sn -2.…”

“…The assay was performed after 72 h of exposure to varying concentrations of the tested agents. The in vitro cytotoxic effect of all agents was examined using the MTT (MV4-11) or SRB assay [ 16 ]. The results were calculated as IC 50 (inhibitory concentration 50%) of the concentration of tested agent, which is cytotoxic for 50% of cancer cells.…”

“…Up to now, Yang and co-workers successfully incorporated ferulic acid into the phosphatidylcholine (PC) structure by chemoenzymatic acidolysis catalyzed by lipase Novozym 435, whereas Prasad research group introduced into sn -1 position of 1,2-dipalmitoylphosphatidylcholine (DPPC) and egg-yolk PC syringic and vanillic acids, obtaining products with increased antioxidant and antimicrobial activities [ 14 , 15 ]. This convinced us to synthesize the novel phenolic-phospholipids conjugates, especially because in our previous project we proved that it is possible to increase the bioavailability and reduce the active dosage of natural compounds like isoprenoids joined to PC [ 16 , 17 ].…”

The N’-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity

“…The assay was performed after 72 h of exposure to varying concentrations of the tested agents. The in vitro cytotoxic effect of all agents was examined using the MTT (MV4-11) or SRB assay [37]. The results were calculated as IC 50 (inhibitory concentration 50%) the concentration of tested agent, which is cytotoxic for 50% of the cancer cells.…”