Nucleic acid binding drugs. Part IV. The crystal structure of the anti-cancer agent daunomycin.

The crystal structure has been determined of the anti-cancer drug daunomycin, as the hydrochloride monohydrate pyridine salt. The overall structure, previously determined by X-ray analysis of an N-bromoacetyl derivative (Anguili, R., Foresti, E., Riva Di Sanserverino, L., Isaacs, N.W., Kennard, O., Motherwell, W.D.S., Wampler, D.L. and Arcamone, F. (1971) Nat. New Biol. 234, 78-80) has been confirmed, although substantial conformational differences are observed. The conformation described here is very similar to that found for the related drug carminomycin I (Wani, M.C., Taylor, H.L., Wall, M.E., McPhaill, A.T. and Onan, K.D. (1975) J. Am. Chem. Soc. 97, 5955-5956; Pettit, G.R., Einck, J.J., Herald, C.L., Ode, R.H. Von Dreele, R.B., Brown, P., Brazhnikova, M.G. and Gause, G.F. (1975) J. Am. Chem. Soc. 97, 7387-7388); it is suggested that this represents a significantly stable molecular conformation; an intramolecular C(7)...O(9) hydrogen bond is invoked to account for this. This conformation is likely to be at least close to that of daunomycin when bound to DNA.