Synthesis and biological evaluation of sparsomycin analogs

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Abstract
Three series of sparsomycin analogs were prepared and examined for their ability to inhibit DNA or protein synthesis in bone marrow, P388 [mouse] lymphocytic leukemia and P815 [mouse] mastocytoma cells. The compounds of series I and II, distinguished by the inclusion or exclusion of a hydroxymethyl functional group, were designed to elucidate the effect on activity of replacing the oxodithioacetal side chain of sparsomycin with 4-substituted benzyl groups. The series III analogs, which excluded the hydroxymethyl group and replaced the oxodithioacetal moiety of sparsomycin with a benzyl amide group, were designed to investigate the potential interaction of an amide oxygen in contrast to the sulfoxide oxygen of sparsomycin. Overall, the bromobenzyl-substituted analogs imparted the greatest inhibitory activity in the protein synthesis assay, while the methoxybenzyl-substituted analogs displayed the least. The methylbenzyl and the unsubstituted benzyl compounds were intermediate in inhibitory potential. The activity in the protein synthesis assay may correspond to the lipophilic and electronic characteristics of the substituents on the benzyl moiety of the analogs. All of the compounds were inactive in the DNA synthesis assay. [Sparsomycin is an antineoplastic drug.].