Combination of experimental and in silico methods for the assessment of the phototransformation products of the antipsychotic drug/metabolite Mesoridazine

Wilde, Marcelo L.; Menz, Jakob; Leder, Christoph; Kümmerer, Klaus

doi:10.1016/j.scitotenv.2017.08.040

Cited by 10 publications

(3 citation statements)

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“…If all relevant end points have been assessed and comply with the defined thresholds, i.e., the molecule is biodegradable, neither bioaccumulative nor (eco)toxic, and its function is ensured, it should be synthesized to perform experimental tests in the wet laboratories to confirm the predicted activities and properties. In addition, if the designed molecule will enter the aquatic environment after the intended use (e.g., pharmaceuticals), it is important to identify and assess (human) metabolites as well as any other (environmental) TPs by either in silico tools or in vitro tests in order to prevent the accumulation of harmful TPs in the environment. ,, …”

Section: Application Of In Silico Tools Within Bbd Approachesmentioning

confidence: 99%

“…In addition, if the designed molecule will enter the aquatic environment after the intended use (e.g., pharmaceut-icals), it is important to identify and assess (human) metabolites as well as any other (environmental) TPs by either in silico tools or in vitro tests in order to prevent the accumulation of harmful TPs in the environment. 33,34,36 There are no case studies published yet that applied the whole workflow as presented in Figure 2. However, there are some studies, which served as a basis for the development of the herein presented workflow.…”

Section: Approachesmentioning

confidence: 99%

“…A combination of in silico tools and experimental testing offers several advantages including priority setting and the selection of the most promising candidates for synthesis and testing . Several studies have shown the feasibility of combining in silico and experimental testing to assess chemicals with unknown properties. ,− These studies revealed that in silico assessment is appropriate for assessing environmental fate and effects of chemicals and products of incomplete mineralization even before their synthesis ,− ,, Consequently, in silico methods allow for fast decisions whether the chemical is a promising candidate for further experimental testing while limiting the digital pool of possible chemicals.…”

Section: Introductionmentioning

confidence: 99%

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Toward Application and Implementation of in Silico Tools and Workflows within Benign by Design Approaches

Lorenz¹,

Amsel²,

Puhlmann

et al. 2021

ACS Sustainable Chem. Eng.

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To avoid adverse side effects of chemicals, pharmaceuticals, and their transformation products (TPs) in the environment, substances should be designed to fully mineralize in the environment at their end-of-life while ensuring a degree of stability as needed for their application. These considerations should be implemented at the very beginning of chemical’s and pharmaceutical’s design (Benign by Design, BbD) to meet requirements set by planetary boundaries and upcoming legal frameworks (e.g., “Chemicals Strategy for Sustainability towards a Toxic-Free Environment” by the European Commission (EC)). In silico tools are already being implemented in the drug discovery process and the assessment of chemicals and pharmaceuticals. The advantage of which is avoiding or at least minimizing animal testing and chemical waste due to experimental testing as well as reducing the time to market. However, in the literature, there are just a few examples of how in silico tools could be implemented in the BbD process. Therefore, this study suggests a workflow supporting practitioners designing new environmentally mineralizing chemicals and pharmaceuticals. This would also result in a much faster and less expensive process than starting with repetitive synthesis and subsequent experimental testing to improve the compounds’ properties.

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Section: Application Of In Silico Tools Within Bbd Approachesmentioning

confidence: 99%

Section: Approachesmentioning

confidence: 99%