Cytotoxic ring A-modified steroid analogues derived from Grundmann’s ketone

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.

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► Steroid analogues with different ring A sizes and functionalities were synthesized.
► Antibacterial, antifungal and cytotoxic activities were tested of all compounds.
► A rigid steroid backbone was found to be indispensable for cytotoxic activities.
► A Michael acceptor system implemented in ring A reinforced cytotoxic activities.
► Selected compounds satisfied NCI pre-determined threshold inhibition criteria.