title: Cytotoxic ring A-modified steroid analogues derived from Grundmann's ketone.
abstract: A series of steroid and azasteroid analogues containing a six-membered ring A with various functionalities were synthesized. Furthermore, the syntheses of tetracyclic analogues bearing a five-membered A-ring and the syntheses of a number of bicyclic secosteroid analogues were carried out. All compounds were tested for their antibacterial, antifungal and cytotoxic activities. Among all tested compounds 7 and 9 showed outstanding cytotoxic activities but were devoid of antimicrobial activities. The cytotoxic activities of compounds 7, 9 and 10 were initially verified by the National Cancer Institute (NCI) in a one-dose 60 cell assay. In accordance with our results 7 and 9 satisfied pre-determined threshold inhibition criteria for progression to the 5-dose NCI screening, which revealed a selective activity profile for both candidates.
authors.affiliation: Department Pharmazie - Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 Munich, Germany. christoph.mayer@cup.uni-muenchen.de
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Mayer
authors.forename: Franz
authors.initials: F
authors.lastname: Bracher
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D052978:Disk Diffusion Antimicrobial Tests; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013256:Steroids / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D007659:Ketones; D013256:Steroids