In silico ecotoxicological evaluation of hydroxylated progesterone biotransformation products generated by the marine-derived fungus Penicillium oxalicum CBMAI 1996

Understanding the environmental behavior of recalcitrant molecules, particularly steroidal compounds, is essential for assessing their long-term ecological impact. The marine environment represents a major sink for substances widely consumed by modern societies, including pharmaceuticals and hormones that tend to bioaccumulate in aquatic organisms and interfere with biological processes due to their intrinsic endocrine activity. Progesterone is a widely used hormone and was therefore selected as the target compound in this study.

Recent studies demonstrated that the marine-derived fungus Penicillium oxalicum CBMAI 1996, isolated from the sponge Chelonaplysilla erecta, promotes progesterone bio-oxidation, yielding three novel hydroxylated products—15β-hydroxyprogesterone (1), 7β,15β-dihydroxyprogesterone (2), and 2β,15β-dihydroxyprogesterone (3)—whose structural elucidation has been previously reported in the literature. In the present work, the computational platforms ECOSAR 2.0 and SwissADME were employed to estimate lipophilicity (log Kₒw) and predict acute and chronic ecotoxicological effects. These validated in silico approaches enable rapid environmental hazard screening and support the interpretation of how enzymatic oxidation may influence the environmental persistence of steroidal contaminants.

Simulations of the derivatives revealed a consistent decrease in molecular lipophilicity, with log Kₒw values of 3.20, 2.25, 2.44, and 4.02 for compounds 1–3 and progesterone, respectively, accompanied by reduced predicted ecotoxicity toward representative aquatic organisms, including fish, daphnids, and green algae. Acute fish toxicity values (LC₅₀, mg L⁻¹) were 121, 506, 164, and 25, whereas predicted chronic toxicity values (mg L⁻¹) were 82, 1030, 137, and 2.6. These findings indicate that microbial hydroxylation substantially alters the physicochemical and toxicological profiles of progesterone-derived products, suggesting a progressive attenuation of environmental risk.

Overall, the predicted reduction in hydrophobicity relative to the parent hormone indicates lower bioaccumulation potential, while ecotoxicological modeling highlights microbial oxidation as a relevant natural process contributing to the environmental attenuation and prospective degradation of persistent steroids in marine ecosystems.