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Curcumin, obtained from turmeric, has several biological properties to make it a desirable template for drug development. A lipophilic derivative of curcumin, diacetyl curcumin (DAC) and a hydrophilic derivative, diglutaryl curcumin (DGC) were synthesized and their in vivo analgesic and anti-inflammatory activities were compared with those of curcumin and aspirin. The in vitro anti-cancer activities of curcumin and the two derivatives against three cell cancer lines were compared with those against a non-cancerous cell line. The inhibitory effects were comparable to each other and nearing that of curcumin while they showed low inhibitory effect towards the non-cancerous cell line. The mouse tail flick assay showed that curcumin, DAC and DGC increased latency time. DGC was most effective as an analgesic, even more so than aspirin. The maximum percentage effect (MPE) was highest with DGC at 3 hours. The carrageenan induced paw edema model indicated anti-inflammatory activity of all three curcumin formulations. The percentage inhibition of paw edema was maximum for DAC, followed by aspirin and curcumin.

Labeled and unlabeled aliphatic and steroid esters of gamma-amino[U-14C]butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15- octadecatrienyl ( linolenyl ), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20- dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl , and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility.

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