The development of sparsomycin as an anti-tumour drug.
The synthesis of sparsomycin and eight lipophilic analogues is discussed. Sparsomycin, a bacterial metabolite, is a potent inhibitor of protein biosynthesis; in addition it has anti-tumour properties. Structure-activity relationship studies indicate that the anti-tumour activity is a direct consequence of the inhibition of protein synthesis. Two of the analogues show a higher anti-tumour activity in vitro as well as in vivo, and are less toxic to mice than sparsomycin. Finally, some properties of sparsomycin are discussed: the drug potentiates the cytotoxicity of cisplatin and is selectively active on tumour cells without affecting human bone-marrow.
Ottenheijm
H C
HC
Laboratory of Organic Chemistry, University of Nijmegen, The Netherlands.
van den Broek
L A
LA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D013033:Sparsomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D013033:Sparsomycin