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Probing natural molecules with PPAR- to reveal potent agonist against Cancer
Špaková, Adriána ; Bhogal, Inderjeet (oponent) ; Roy, Sudeep (vedoucí práce)
The work focuses on searching for a natural molecule with potential agonistic properties against cancer. The aim of the work was primarily to understand the connection between the peroxisome proliferator-activated receptor gamma (PPAR-) and cancer. Subsequently, molecules from six databases were virtually screened and docked to nuclear receptor PPAR- by using computer aided drug design approach. Hits underwent further exploration, including a dynamic simulation and binding free energy study. Safety verification of the best molecules was performed by ADMET prediction models. An important part of the work was the comparison of newly discovered molecules possessing agonistic properties against cancer with those already known on the market. Specifically, Troglitazone and Rosiglitazone have served as standards, characterized by their high affinity to the PPAR- receptor and demonstrated antineoplastic effects in various human malignant tumors, including breast, colorectal, and pancreatic cancer. On the other hand, these two synthetic molecules face a warning from the FDA (Food and Drug Administration) due to their adverse side effects. Within the study, natural molecules with better properties than the current standards have been discovered. These promising results deserve further attention. One of these molecules could potentially lead to the development of a new drug.
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