Structure-activity relationships of sparsomycin and its analogs: octylsparsomycin: The first analog more active than sparsomycin

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Abstract
Nine analogs of sparsomycin (1) were synthesized; their cytostatic activity was studied in an in vitro clonogenic L1210 [mouse leukemia cells] assay by measuring the inhibition of colony formation. The activity of an analog, expressed as an ID50 [50% inhibitory dose], was compared to that of 1. Each analog possessed not > 2 structural modifications of 1. Comparison of the activity of 1 with that of 3 stereomers, having RCSS, SCSS and RCRS chirality, respectively, showed that the S configuration of the chiral C atom is essential for an optimal activity. The R chirality of the sulfoxide S atom of sparsomycin is important. Study of the ID50 values of S-deoxo analog and compounds having the B-sulfoxide function indicated that the presence of an O atom on the .alpha.-S atom is essential. Isomerization of the trans double bond into the cis double bond yielded isosparsomycin, which had a low activity. The cytostatic activity of sparsomycin seems to be related to its lipophilicity: octylsparsomycin was 3 times as effective as sparsomycin.

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