The structures of two potential antitumor steroid--base adducts.
Steroids have been coupled to pyrimidines to give potentially target-specific anti-tumor agents. We report here on the molecular structures of two such adducts. 21-(1H-uracil-1-yl)-pregn-4-ene-3,20-dione and 21-(1H-thymin-1-yl)-pregn-4-ene-17 alpha-ol-3,20-dione. The structures of these have been determined by X-ray crystallographic techniques. The uracil substituent of the former compound is observed to be oriented below the alpha-face in the plane of the steroid skeleton. In contrast, upon introduction of a 17 alpha-hydroxyl group, as in the latter compound, the base substituent is found to be in a perpendicular orientation bent towards the beta-face of the steroid skeleton. In the uracil derivative the bases stack between steroid portions of other molecules. In the thymine adduct this does not occur. Only steroid--steroid stacking is observed. The molecule conformations are correlated with the differences in receptor affinity for these two steroid adducts.
D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D006860:Hydrogen Bonding; D006908:Hydroxyprogesterones / Q000378:metabolism; D008968:Molecular Conformation; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013329:Structure-Activity Relationship; D013941:Thymine / Q000031:analogs & derivatives* / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D006908:Hydroxyprogesterones; D011987:Receptors, Steroid; C038350:uracil-progesterone; D011374:Progesterone; D014498:Uracil; C038351:thymine-hydroxyprogesterone; D013941:Thymine