ABSTRACT
One of the approaches to enhance bioavailability of nucleoside reverse transcriptase HIV inhibitors consists in design of their prodrugs based on 1,3-diacylglycerols, which may simulate nature lipids metabolic pathways promoting the improvement of drug delivery to the target cells. Glycerolipidic AZT conjugates with different functional phosphoric centers were synthesized by H-phosphonate technique in the present work. Study of prepared prodrugs sensibility to the chemical and enzymatic hydrolysis (in buffer solution and under the influence of pancreatic lipase) and also study of their anti-HIV activity on the T-lymphoid human MT-4 cells in regarding to virus HIV-1(899A) strain were carried out.
Subject(s)
Anti-HIV Agents/chemical synthesis , HIV-1/drug effects , Zidovudine/chemical synthesis , Zidovudine/pharmacology , Anti-HIV Agents/chemistry , Cell Culture Techniques , Drug Delivery Systems , HIV Infections/drug therapy , Humans , Phosphorus/chemistry , Prodrugs/chemical synthesis , Prodrugs/chemistry , Prodrugs/pharmacology , Zidovudine/analogs & derivativesABSTRACT
Contents of sphingolipids (ceramide, sphingomyelin, gangliosides) and the composition of their sphingoid bases were studied in the transplantable rat nephroma-RA and in rat kidneys. The content of sphingomyelin was about 1.3-fold decreased and the content of ceramide was about 1.4-fold increased in the nephroma compared to normal kidneys, and this correlated with a 1.4-fold increased activity of neutral sphingomyelinase; however, the activity of the acidic isoform of the enzyme was virtually unchanged. The content of gangliosides was also increased in the nephroma. Ceramide and sphingomyelin of the nephroma, in addition to sphingosine, contained a significant amount of sphinganine, although a considerable amount of the latter was also found in the renal ceramide. The ratio sphingosine/sphinganine in sphingomyelins changed from 65:1 in kidneys to 5:1 in the nephroma. Thus, the biosynthesis of sphingoid bases seems to be disturbed in the transplantable rat nephroma-RA compared to normal kidneys.
Subject(s)
Kidney Neoplasms/metabolism , Sphingolipids/metabolism , Animals , Apoptosis , Cell Division , Ceramides/metabolism , Gangliosides/metabolism , Kidney Neoplasms/pathology , Neoplasm Transplantation , RatsABSTRACT
The paper summarizes own results of studies on phospholipids and glycolipids from natural biological sources. New approaches for synthesis of inositol-containing sphingophospholipids, glycophosphatidylinositols, semisynthetic synthesis of phosphoglycerols have been introduced. New industrial method of phosphjatidylcholine isolation and production of number of lipid preparations were developed. Incorporation of DOPA into liposomes increases efficacy of its action in the medication of MPTP-induced parkinsonism in mice.
