Drug-like properties of serial phenanthroindolizidine alkaloid compounds: ADMET characteristic prediction and validation

Phenanthroindolizidine alkaloids (PAs) are a series of compounds that have been isolated from traditional herbal medicines and have significant therapeutic potential, such as anti-arthritic, anti-viral, anti-inflammatory, and anti-glioma effects in vitro and in vivo. This study aimed to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics of 44 compounds in silico and to verify the ADMET characteristics. The 2-dimensional structures of these compounds were generated using ChemDraw and the characteristics were predicted using ADMET Predictor™ software. Key characteristics, such as pKa, logP/logD, solubility, permeability, absolute bioavailability in rats, and preliminary toxicity, were measured on some typical compounds to verify the accuracy of the prediction results. The results showed that ADMET predicts physicochemical and biological properties quickly and accurately for PAs. PAs are biopharmaceutics classification system (BCS) class IV compounds with low bioavailability. Moreover, these compounds have higher lipophilicity and are easily distributed into the brain after oral administration to treat brain diseases. However, some of these compounds exhibited colonic toxicity. To improve the drug-like availability of these compounds, more in-depth research should be conducted on drug delivery systems.