Antihormonal potential of selected D-homo and D-seco estratriene derivatives

• New D-homo and 16,17-seco-estratriene compounds were synthesised and characterized.
• Docking studies were performed for protein targets of steroidal anti-cancer drugs.
• Estrogen and antiestrogen activity of the new compounds was determined.
• X-ray structural analysis of a new compound was performed.
• Some compounds partially inhibit 17,20 lyase, while some activated aromatase.

Since many estrogen derivatives exhibit anti-hormone or enzyme inhibition potential, a large number of steroidal derivatives have been synthesised from appropriate precursors, in order to obtain potential therapeutics for the treatment of hormone-dependent cancers. In molecular docking studies, based on X-ray crystallographic analysis, selected D-homo and D-seco estratriene derivatives were predicted to bind strongly to estrogen receptor α (ERα), aromatase and 17,20 lyase, suggesting they could be good starting compounds for antihormonal studies. Test results in vivo suggest that these compounds do not possess estrogenic activity, while some of them showed weak anti-estrogenic properties. In vitro anti-aromatase and anti-lyase assays showed partial inhibition of these two enzymes, while some compounds activated aromatase. Aromatase activators are capable of promoting estrogen synthesis for treatment of pathological conditions caused by estrogen depletion, e.g. osteopenia or osteoporosis.

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