Pharmacokinetic profiling of anticancer phytocompounds using computational approach

Introduction: Natural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process. Objective: With a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant-based anticancer compounds, open-access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability. Methodology: Our workflow involved identification of molecules capable of passing each of the ADMET barriers based on physicochemical properties of molecules, and physiological barriers and factors. Results: The results revealed that out of 5086 phytomolecules, 63% were orally absorbable and 52% distributable. Also, an appreciable proportion of these compounds (45%) could be metabolised and excreted. Furthermore, 28% were found to be non-toxic for cardio toxicity and central nervous system (CNS) activity. Additionally, comparison against known anticancer drugs (reference dataset) revealed that the three libraries exhibit similar trends, thus providing additional confidence to the predictions. Overall, 28% of the molecular dataset was found to have suitable pharmacokinetic properties. We have also discussed a few natural products which exhibit favourable ADMET as well as low nano-micromolar in vitro anticancer activity. Conclusion: We have created an interactive database (ADMETCan), which provides access to predicted ADMET of these anticancer phytomolecules. The ease of availability of this dataset is expected to minimise failure rate of these compounds and thus is expected to be beneficial to the scientific community involved in anticancer identification and development.