Biomedical subjects

S D Wyrick

Publications and source records attributed to S D Wyrick.

58 records · Page 4Linked to original sources

PubMed1976

Hypocholesterolemic activity of 1,3-bis(substituted phenoxy)-2-propanones.

A series of 1,3-bis(substituted phenoxy)-2-propanones was found to be active hypocholesterolemic agents at 10 mg/kg/day. The p-chloro- and p-methyl-substituted phenoxy compounds possess the highest activity. These compounds did not possess the estrogenic and antifertility activities of the related previously reported derivatives of the bis(beta-phenylethyl) ketone series. The 1,3-bis(p-methylphenoxy)-2-propanone (7) also lowered serum triglycerides and glycerol which appeared to be due to increased levels of serum lipase and reduced activity of liver lipase. There was reduced incorporation of free fatty acids into complex lipids by the liver. Cholesterol was excreted faster in the treated animals.

Animals↗

PubMedDate not supplied

The disposition of the hypolipidemic agent, o-(N-phthalimido)acetophenone, in Sprague-Dawley rats.

Disposition studies of the potent experimental hypolipidemic agent, o-(N-phthalimido)acetophenone, were conducted in the laboratory rat. Intravenous administration of the drug demonstrated a declining biphasic plasma concentration-time curve suggesting a rapid distribution into tissues. Less than 5% of the intravenous dose was recovered in urine and feces after 5 days. Oral administration of the drug showed that the maximum blood levels were attained within 15 min. After 48 hr, 92% of the orally administered 14C dose was eliminated either via urine (60%) or feces (40%). 14C in a 0-24-hr urine collection after oral administration showed that urinary radioactivity was composed of 22% of the parent compound o-(N-phthalimido) acetophenone, a benzoic acid metabolite (22%) o-(N-phthalimido)benzoic acid, and an amic acid metabolite (56%) N-(o-acetophenone)phthalamic acid. The two metabolites were unconjugated and possessed less hypolipidemic activity than the parent drug.

Acetophenones↗

PubMedDate not supplied

The cytotoxicity of [(N-alkyl-1H,3H-1-oxoisoindoline-5-yl-oxyl alkanoates and related benzamides in murine and human tissue cultured cell lines.

Substituted oxoisoindolines are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 16 at both regulatory enzymes, i.e. PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. The agent lowered d(GTP) and d(CTP) pool levels, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 16 for 24 hr at 100 microM and some undefined interaction between the drug and the nucleoside bases appeared to occur, lowering DNA synthesis and causing cell death.

Amidophosphoribosyltransferase↗

PubMedDate not supplied

The cytotoxicity of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]-alkanoic acids in murine and human tissue cultured cell lines.

Substituted isoindoline-1,3-diones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, colon, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 4 at both regulatory enzymes, i.e. PRPP amido transferase and IMP dehydrogenase. The agent lowered d(GTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 4 for 24 hr at 100 microM, lowering DNA synthesis and causing cell death.

Amidophosphoribosyltransferase↗