Title : Steroid estrogen analogues as potential drugs with targeted action
Abstract:
Steroid estrogens being sex female hormones play crucial role in the functioning of male and female organisms. After menopause, the estrogen level is tragically decreased that causes many disorders like osteoporosis, dementia and cancer development. In this presentation, we will discuss about new modified analogues of steroid estrogens which have been developed in our group as osteoprotectors, cardioprotectors and anti-cancer agents. We present the data covering many aspects of drug design: molecular docking, total synthesis details, pre-clinical investigations, structure-biological activity relationship. New data in the field of most perspective area - the inhibitors of estronesulfatase as new anti-cancer agents - also will be discussed. The developed potential drugs have the improved biological profile in comparison with clinically used medications. At the same time, they have targeted activity which equal or higher compared to known clinically used compounds. We found analogues with high esteoprotective action and decreased hormonal activity, which are perspective molecules for hormone replacement therapy. The analogues with high cardioprotective activity and without hormonal activity are the best candidates for the prevention and treatment of cardio-vascular diseases. The developed estrogen analogues with high (comparable to endogenous estradiol) antioxidant activity may be very useful for the treatment of neurodegenerative diseases like Alzheimer. On the basis of experimental data we developed the model for the prediction of antioxidant activity. We also demonstrated the possibility of the creation of hybrid molecules with synergic action. These compounds highly active against prostate and breast cancers. For the first time, we illustrated that modified estrogens may be active against triple-negative breast cancer cells.
Takeaway Notes:
• New data about modified estrogen analogues as potential medications with targeted action.
• The knowledge about drug design approaches in the field of modified estrogen analogues.
• Molecular docking as effective tool for the introduction of modifications in steroid skeleton for the selectivity of action.
• The presented data will be useful for scientists working in drug design and application, mainly in the field of anticancer agents and hormone-replacement therapy.
• Most of all data in the presentation are new and not published yet. The data may be used as basis for lecture courses and practice illustration of the development of medications with targeted activities. New ideas about the different applications of the developed drugs in other areas may arise. The potential drugs may be useful for the creation of new hybrid molecules with enhance activity.
• The presented results may be used for researchers for clinical application, pre-clinical investigations as well as for the consideration of the creation of new formulations and conjugates which may be new platform for the drugs with high effective targeted action. The data may be used also for students and PhD students as illustration of drug design and application.
• The pre-clinical data obtained illustrate the high effectiveness of new analogues as compared with approved mediations and the efficacy and safety are much better as it is known.
• The therapeutic significance of estrogens is quite broad, and thus the obtained new perspective molecules may be investigated in various assays and models in other research groups to extend and to share the knowledge about new properties of estrogen analogues.
