Abstract
Background/Objectives: Steroids have demonstrated selective cytotoxic properties against tumor cells. The pro-gesterone receptor (PR) plays a vital role in the proliferation, cell differentiation, and maintenance of female reproductive tissue, and its malfunction can lead to breast cancer. The use of the biocatalytic method by filamentous fungi has sparked interest in the obtained of steroids due to the advantages of the process. Methods: Pharmacokinetic and toxicological properties (rat and mouse), molecular docking simulation studies, and prediction of the spectrum of biological activity were performed to select molecules with the potential for PR inhibition, from 155 biotransformed products of the progesterone. Subsequently, the chemical structures were subjected to an evaluation of their pharmacokinetic and toxicological properties and, with the application of ADMET filters. Results: Androstenedione, 17α-hydroxyprogesterone, and dihydrotestosterone, obtained by the process of biotransformation of PR by different filamentous fungi, showed good pharmacokinetic profiles and low toxicity compared to the control groups. The in-silico data associated with molecular docking studies revealed the best binding affinity and similarity in the interactions of these molecules against the human progesterone receptor target. Thus, the results of biological activity spectrum prediction highlight the great potential to investigate the role of molecular descriptors in the attribution of anti-cancer activities. Conclusions: The biocatalytic process, by filamentous fungi, can provide important molecules as a product of progesterone biotransformation, such as androstenedione, 17α-hydroxyprogesterone, and dihydrotestosterone. In this study we showed that these molecules have good pharmacokinetic profiles and low toxicity for antineoplastic activity (breast cancer).