Alkaloids are organic compounds that contain at least one nitrogen atom, usually bound within a heterocyclic structure. As the name suggests, alkaloids generally exhibit basic properties, although some alkaloids do not possess basic characteristics. They occur naturally in plants, fungi, and animals. Humans are exposed to them daily through the food chain, the use of medications, or other sources. While alkaloids display numerous beneficial properties, they can also be toxic. Given the recent increase in research into endocrine-disrupting chemicals, it is reasonable to explore the potential effects of alkaloids on the endocrine system. Current studies indicate that some alkaloids may act as potential endocrine disruptors.
Endocrine Disruptome (ED) is a freely accessible software platform that enables in silico evaluation of ligand binding to nuclear hormone receptors. In this master's thesis, we used this publicly available program to assess the endocrine activity of 43 selected alkaloids. From among many true alkaloids, representatives from different chemical groups were randomly selected. The results were divided into three groups based on whether the program classified them as highly or moderately likely endocrine disruptors (placed in the red or orange binding class), whether they are already recognized in the literature as potential endocrine disruptors, or whether the compounds did not fall into either of the aforementioned categories. Among the 43 studied alkaloids, only nicotine has already been confirmed as an endocrine disruptor. The program classified as many as 20 alkaloids into the red or orange binding class for at least one receptor, most commonly androgen receptors. The most predicted interactions were with androgen, estrogen, and thyroid receptors. Quinolizidine alkaloids emerged as the chemical group with the highest affinity for nuclear hormone receptors.
Since experimental data on the effects of randomly selected alkaloids on the endocrine system are extremely scarce, the predictive power of the program cannot be fully evaluated. Additional, more complex in vitro and in vivo methods would be required to confirm the obtained results. The Endocrine Disruptome program is accepted by regulatory agencies (European Chemicals Agency, European Food Safety Authority) for the prediction of endocrine activity and serves as an appropriate software tool for identifying potential endocrine disruptors, particularly when used in combination with other in vitro and in vivo testing methods.
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