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At least 19 recordsLinked to original sources
PubMed1997

Tartronates: a new generation of drugs affecting bone metabolism.

In the search for a new class of bone-sparing agents for treating osteopenic disorders, we hypothesized that tartronic acid derivatives, sharing the chemical characteristics both of bisphosphonates and of Gla residues contained in matrix proteins such as osteocalcin, could positively affect bone metabolism. A series of tartronates was therefore tested for their ability to affect bone metabolism. In vitro resorption tests were performed examining pit formation by freshly isolated rat and rabbit osteoclasts plated onto bone slices and exposed to the drugs for 48 h. Tartronates bearing a linear side-chain (DF 1222 and DF 1363A) were the most effective in inhibiting pit excavation in the pM-nM range. Tartronates did not affect osteoclast viability, number, adhesion, or tartrate resistant acid phosphatase activity. Transient cell retraction was observed in osteoclasts plated onto glass and exposed to DF 1222. The maximal effect was seen in cells treated for 4 h at a concentration of 1 pM. DF 1222 accelerated mineralization in cultures of periosteal cells without affecting other osteoblast-like functions. This product was therefore tested in vivo in ovariectomized mice. Bone mass in femur was evaluated, by ash gravimetry, 21 days after ovariectomy. Unfortunately, DF 1222, the most active of tartronates in vitro, was inactive in this test because of its high hydrophilicity and the subsequent too short residence time. On the contrary, its tetrahydropyranyl ether derivative, DF 1363A, endowed with a significantly higher lipophilicity, showed a dose-dependent bone-sparing effect when administered subcutaneously at 10, 30, and 100 mg/kg/die, thus confirming the activity seen in in vitro tests. Because of their feasible parallel effect on both bone resorption and formation, tartronate derivatives may be tested to candidate this class of products for clinical studies.

Animals↗
PubMed1987

Polymers for biodegradable medical devices. III. Polymerization and copolymerization of cyclic derivatives of tartronic acid.

The syntheses of anhydrosulphite and anhydrocarboxylate derivatives of tartronic acid are described. These compounds, more correctly named 5-carboxy-1,3,2-dioxathiolan-4-one-2-oxide and 5-carboxy-1,3-dioxolan-2,4-dione have been shown to undergo polymerization and copolymerization to poly-alpha-esters containing the tartonic acid residue, characterized by the presence of a pendant carboxyl group. Thermal polymerization of the anhydrosulphite appears to proceed in a substantially identical manner to other members of the series in which the monomer decomposes by a first order process to yield an alpha-lactone which polymerizes by a rapid chain growth reaction. Because the rate of thermal polymerization of tartronic acid anhydrosulphite is much more rapid than simple alkyl substituted anhydrosulphites, copolymerization favours the former residues. More successful copolymerization was achieved by the use of tertiary base initiators and the anhydrocarboxylate derivative of tartronic acid. The polymers and copolymers described are of potential value in the synthesis of drug-carrying biodegradable matrices or more hydrophilic analogues of poly(glycolic acid) which combine the known bioerodibility of the moiety with that presence of a pendant carboxyl group.

Biocompatible Materials↗
PubMed1989

Enzymatic synthesis and inhibitory characteristics of tartronate semialdehyde phosphate.

The immediate product of the pyruvate kinase catalyzed phosphorylation of beta-hydroxypyruvate is the enol of tartronate semialdehyde phosphate (TSP). The reaction has the same pH profile as that for the phosphorylation of pyruvate with pK's of 8.2 and 9.7 observed in H2O. This enol tautomerizes in solution to the aldehyde, which in turn becomes hydrated. 31P NMR spectra indicate that the enol resonates approximately 1 ppm upfield from the hydrated aldehyde. By following the tautomerization spectrophotometrically at 240 nm, we have found it to be independent of pH (0.2 min-1 below pH 6 in water), except that it is 2-fold slower above the pK of the phosphate group (6.3 in H2O and 6.7 in D2O). It is 3.6-fold slower in D2O. When this TSP is reduced with NaBH4, approximately 50% of the product is D-2-phosphoglyceric acid (substrate for enolase). Thus, while the immediate product of the phosphorylation rection is the enol of TSP, the eventual product is D,L-TSP. Both the enol and the aldehyde forms of TSP were found to be potent inhibitors of yeast enolase with apparent Ki values of 100 nM and 5 microM, respectively. However, since the aldehyde form is 95-99% hydrated [Stubbe, J., & Abeles, R. (1980) Biochemistry 19, 5505], the true Ki for the aldehyde species is 50-250 nM. The enol of TSP shows slow binding behavior, as expected for an intermediate analogue, with a t1/2 for this process of approximately 15 s (k = 0.046 s-1) and an initial Ki of approximately 200 nM.

Cadmium↗
PubMed1989

[Antilithogenic action of dehydroxymaleic, ketomalonic (mesoxalic) and tartronic acids in relation to experimental lithiasis in rats].

The authors study the effects of three acids, one with four carbon atoms, dihydroxymaleic acid, the two others with three carbon considered atoms, ketomalonic acid and tartronic acid. A first study considered the effects of these products on experimental lithiasis induced by oxalic acid, glyoxylic acid and ethylene-glycol. Dihydroxymaleic acid. Monohydrate calcium oxalate stones can be easily induced in the male rat, with in 24 hours, by an intraperitoneal injection of oxalic acid, at the rate of 8 mg per 100 g of body weight. If 25 mg of dihydroxymaleic acid are injected simultaneously via the intraperitoneal route, to a rat weighing 150 g, the lithiasis observed after 24 hours is just as severe. Experimental monohydrate calcium oxalate lithiasis is also induced by intraperitoneal injection of 8 to 9 mg of glyoxylic acid in a 100 mg rat. Dihydroxymaleic acid, injected at the same time as glyoxylic acid, also via the intraperitoneal route, at the rate of 50 mg for a rat weighing 150 g, results in total suppression of the lithiasis. Dihydroxymaleic acid also prevents lithiasis induced by the absorption by the rat, for several weeks, of a 1% ethylene-glycol solution if it is mixed to this solution at the rate of 5 mg per ml. A 12% ethylene-glycol solution given to the rat at the rate of 0.55 ml for 100 g of body weight induces the next day a comatose state and a diffuse parenchymatous monohydrate calcium oxalate lithiasis: coma and lithiasis are prevented by the simultaneous absorption of dihydroxymaleic acid at the rate of 65 to 70 mg. The ketomalonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗