Degradation of imatinib mesylate by manganese peroxidase (MnP): Optimization, identification of transformation products, pathway proposal and in silico predictions

Abstract

Imatinib (IMB) is an antineoplastic agent used as kinase inhibitor in the treatment of chronic myeloid leukemia. IMB can introduce endocrine and mutagenic disrupting effects, which could adversely impact the environmental due to its commercialization and expanded use in recent years. The fungal ligninolytic enzyme manganese peroxidase (MnP) is a powerful oxidant agent that oxidizes Mn2+ to Mn3+ and promotes degradation of organic pollutants as pharmaceuticals. In this work, the efficiency of MnP for degradation of IMB in distilled water (DW) and simulated wastewater (SW) was evaluated. As a first stage, the experimental condition was optimized using the Doehlert design, response surface methodology, and the desirability profile. The results demonstrated that 1.12 U L-1 of MnP, 1.87 mmol L-1 of hydrogen peroxide, and 0.755 mmol L-1 of Mn2+ created optimal conditions within 4 h of enzymatic treatment in both aqueous matrices. The IMB degradation in both study matrices was observed within a reaction time of 8 h, achieving degradation percentages of 68% ± 4 in DW and 47% ± 7 in SW by the end of the experiment. Control experiments were also conducted to verify the synergy between MnP, Mn ions, and H2O2 on degradation experiments. Sixteen new transformation products (TPs) were elucidated by LC-QTOF MS using two diverse and complementary chromatographic methods. According to (Q)SAR tools, most of the TPs showed the development of toxicity and no biodegradability characteristics; however, the mutagenicity potential decreased compared to the parental IMB, which is an encouraging result considering the mutagenic characteristic of IMB.