Therapeutic effects of D‐aspartic acid β‐hydroxamate (DAH) on friend erythroleukemia

Abstract

D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV-P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.

Proton Dissociation Energies of Zinc-Coordinated Hydroxamic Acids and Their Relative Affinities for Zinc: Insight into Design of Inhibitors of Zinc-Containing Proteinases

“…Hydroxamic acids, best known as iron chelators, have recently been widely used as a key functional group of potential therapeutics targeted at zinc proteinases such as matrix metalloproteinases involved in cancers 2-22 and at other drug targets associated with cardiovascular diseases, − AIDS, − and Alzheimer's disease . It has long been assumed that acetohydroxamic acid can exist in the keto and iminol forms and that each can be present in either the E or Z configuration about the C−N bond .…”

Antioxidant and Amine Oxidase Inhibitory Activities of Hydroxyurea

“…37) The aspartic acid -hydroxamate exhibited antitumor activity on L5178Y leukemia, 38) and had therapeutic effects on friend erythroleukemia. 39) The monohydroxamates of aspartic acid and glutamic acid were also reported to exhibit antioxidant and angiotensin converting enzyme inhibitory activities. 35) The amino acid derivatives of HU were reported to have specific cytotoxicity against murine leukemia and tumor cell lines.…”

Immobilized Zinc Affinity Chromatography of Pectin Hydroxamic Acids for Purification of Trypsin Inhibitors from Soybean and Sweet Potato

“…Oxal hydroxamic acid derivatives are potent inhibitors of matrix metalloproteinases (4). The aspartic acid β-hydroxamate exhibits antitumor activity on L5178Y leukemia (5), therapeutic effects on friend erythroleukemia (6), and antiproliferative activity on friend virus-infected erythropoietic progenitor cells (7). We also reported that pectin hydroxamic acids (PHAs) at different degrees of esterification (DE) exhibited both semicarbazidesensitive amine oxidase and angiotensin converting enzyme (ACE) inhibitory activities (8).…”