Syntheses and cytotoxicity of phosphatidylcholines containing ibuprofen or naproxen moieties

Abstract

In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis conditions, the attached drug moieties racemized, which resulted in the formation of phospholipid diastereomers. The comperative studies of the cytotoxicity of ibuprofen, naproxen and their phosphatidylcholine derivatives against human promyelocytic leukemia HL-60, human colon carcinoma Caco-2, and porcine epithelial intestinal IPEC-J2 cells were carried out. The results of these studies indicated that phospholipids with NSAIDs at both sn-1 and sn-2 positions (15 and 16) were more toxic than ibuprofen or naproxen themselves, whereas 2-lysophosphatidylcholines (7 and 8) were less toxic against all tested cell lines. Phospholipids with NSAIDs at sn-1 and palmitic acid at sn-2 (9 and 10) were also less toxic against Caco-2 and normal cells (IPEC-J2).

Dexibuprofen Therapeutic Advances: Prodrugs and Nanotechnological Formulations

“…The obtained results confirmed presented in the literature data indicate that phospholipid derivatives of active compounds are less cytotoxic than the compounds themselves and that phospholipids could be used also as an effective carriers of NSAIDs [57,58]. New approach for the synthesis of prodrugs of DXI was presented by Kłobucki and coworkers [56]. They obtained a series of novel phosphatidylcholines 13-16 containing dexibuprofen in their structures (Figure 9), which were subsequently evaluated towards two cancer cells (HL-60 and Caco-2) and normal iporcine epithelial intestinal (PEC-J2) cells.…”

“…New approach for the synthesis of prodrugs of DXI was presented by Kłobucki and coworkers [ 56 ]. They obtained a series of novel phosphatidylcholines 13 – 16 containing dexibuprofen in their structures ( Figure 9 ), which were subsequently evaluated towards two cancer cells (HL-60 and Caco-2) and normal iporcine epithelial intestinal (PEC-J2) cells.…”

“…Different approximations have been carried out in order to use DXI for ocular drug delivery. Mixing of DXI with surfactants or other compounds to increase DXI solubility is a practical approach, such as the research carried out by Zhong-Kun and colleagues who New approach for the synthesis of prodrugs of DXI was presented by Kłobucki and coworkers [56]. They obtained a series of novel phosphatidylcholines 13-16 containing dexibuprofen in their structures (Figure 9), which were subsequently evaluated towards two cancer cells (HL-60 and Caco-2) and normal iporcine epithelial intestinal (PEC-J2) cells.…”

Lipase Catalyzed Acidolysis for Efficient Synthesis of Phospholipids Enriched with Isomerically Pure cis-9,trans-11 and trans-10,cis-12 Conjugated Linoleic Acid

“…Nowadays, due to biocompatibility and biological function of natural PLs, the production of phospholipid conjugates with drugs [3,4] and other biologically active compounds-such as isoprenoid [5][6][7], lipoic [8], and phenolic acids [9,10]-is an extensively employed approach. This type of phospholipid conjugate plays a role of lipophilic prodrug where glycerophosphocholine is esterified in sn-1 or sn-2 position with the biologically active molecules, mainly with those that do not occur 2 of 22 naturally in the phospholipid structure.…”

“…This isomer is produced together with the former one with equimolar ratio [29]. 1 enzyme load with respect to the total weight of substrates; 2 92% purity; 3 70.9% purity; 4 67.1% purity; 5 80% purity; 6 77.6% purity; 7 71% purity; 8 99.0% purity; 9 CLA concentrates obtained from sunflower oil: 57.1% t10,c12 CLA, 35.2% c9,t11 CLA and safflower oil: 58.1% t10,c12 CLA 33.9% c9,t11; nd, not determined; CLAEE, conjugated linoleic acid ethyl ester; GPC, sn-glycero-3-phosphocholine; INC, incorporation of CLA; EINC, effective incorporation of CLA (Equation (3)).…”