Biomaterial Database

Cytotoxicity of pivoxil esters of antiviral acyclic nucleoside phosphonates: adefovir dipivoxil versus adefovir. 2005

Zdenĕk Zídek, and Eva Kmonícková, and Antonín Holý

Institute of Experimental Medicine, Academy of Sciences, Vídenská 1083, Prague, Czech Republic. zidekz@biomed.cas.cz

Biological effectiveness of antiviral acyclic nucleoside phosphonate adefo vir, 9-[2-(phosphonomethoxy)ethy]ade nine (PMEA) and its more lipophilic (bis)pivaloyloxymethyl ester prodrug adefovir dipivoxil (bis-POM-PMEA) were compared under in vitro conditions in mammalian cell systems. Proliferation of murine splenocytes was inhibited in a concentration-dependent manner, the bis-POM-PMEA being more effective than PMEA. In contrast to PMEA, bis-POM-PMEA inhibited production of nitric oxide (NO) in macrophages activated with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Viability of both splenocytes and macrophages remained uninfluenced by PMEA, whereas pronounced cytocidal effects were exhibited by bis-POM-PMEA. The IC(50)s reached the values of 15 microM and 30 microM in cultures of macrophages and splenocytes, respectively (assayed at the interval of 24 hrs). The effects could partly be mimicked by formaldehyde, a decomposition product of the pivoxil moiety of bis-POM-PMEA. The other possible product, pivalic acid, was ineffective in this respect. The present data are consistent with the view that pivoxil prodrug of PMEA, bis-POM-PMEA possesses enhanced but also broader spectrum of biological effects than the parent compound.

UI	MeSH Term	Description	Entries
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D011355	Prodrugs	A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.	Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D005260	Female		Females
D000225	Adenine	A purine base and a fundamental unit of ADENINE NUCLEOTIDES.	Vitamin B 4,4, Vitamin B,B 4, Vitamin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia