| Abstract
| - A series of four structurally related carbocyclic nucleosides(6a, 6b, 10a, and 10b)weresynthesized and evaluated for their ability to inhibit tumor necrosisfactor-α (TNF-α),interleukin-1β (IL-1β), and interleukin-6 (IL-6) production fromhuman primary macrophages.These compounds had little effect on the production of IL-1β andIL-6. It was determined thatcompound 10a was the most potent inhibitor of TNF-αproduction (IC50 = 10 μM), having 2−5-fold more activity compared to its enantiomer 10b or itsdiastereomers 6a and 6b. Inaddition,these compounds were also tested for their ability to protect miceagainst lethal challenges oflipopolysaccharide (LPS) and d-galactosamine(d-Gal). Compound 10a showedsuperiorprotective effects (100% protection) compared to its enantiomer10b or its diastereomers 6aand 6b when it was administered to mice which werechallenged with 3 times the LD100 doseof LPS.
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