In addition to adequate pharmacological efficacy and safety profile, a balance of optimized bioavailability and reduced drug interactions potential maximizes the chance of a natural product becoming a successful therapy. Drug metabolism and pharmacokinetic (DMPK) screening must be evaluated firstly in vitro, which provides pharmacological orientation for in vivo design studies. Considering the demand for innovative products from Brazilian biodiversity, a platform for preclinical studies of natural products was developed by our research group, in which in vitro DMPK assays were applied to lead compounds with highlighted in vitro pharmacological activity such as seriniquinone (marine natural product), specioside, casearin X and licarin A (plant natural products). The compounds were evaluated for determination of its lipophilicity (shake-flask method), permeability (Caco-2 cells monolayer system), plasma protein binding (ultracentrifugation), metabolites survey (Human Liver Microsomes – HLM; metalloporphyrins; Electrochemistry-Mass Spectrometry) and kinetic parameters of metabolism, phenotyping and drug interactions studies (HLM) - Table 1.

Table 1 – In vitro DMPK main results obtained for seriniquinone, specioside, casearin X and licarin A.

*Performed in intact Caco-2 cells system / Caco-2 cells with carboxylesterases inhibited.

This platform provides a data panel that allows identifying key areas in which properties of compounds needs to be improved or to proceed through in vivo PK. Thereby, in vitro DMPK screening for potential compound classes allows the researcher team to rank order of molecules not only based on their potency, but also in relation to the predicted bioavailability, which is crucial for the advance on drug discovery and development from natural sources.