Drug Development of Kenyan Herbal Medicine: In Silico Evaluation and Prediction of Novel Derivatives of Polygonum Senegalense Chalcone Extracts as Anti-Cancer Agents

Abstract

Chalcones are versatile, reactive a, b-unsaturated -unsaturated cyclic aromatic molecules that can be synthetically modified and optimized into drug-like molecules. In the present study, in silico cytotoxicity prediction, Physicochemical, Pharmacokinetic, ADME (Absorption, Distribution, Metabolism, and Excretion), and Medicinal Chemistry evaluation analyses were carried out on heterocyclic derivatives of Polygonum senegalense chalcones.  Cell line cytotoxicity prediction based on Prediction of Activity Spectra for Substances (PASS) technology was performed, and the training set was created based on cytotoxicity data retrieved from the Chemical Database of Bioactive Molecules (ChEMBLdb). In addition, estimation of absorption, distribution, metabolism, and excretion (ADME) using physicochemical, drug-likeness, pharmacokinetics, and medicinal chemistry properties was carried out. The highest cytotoxicity of the molecules revealed Pa values of about 0.7 in targeted cancer cell lines that included ovarian adenocarcinoma, breast carcinoma, renal carcinoma, and glioblastoma, underscoring the therapeutic potential of chalcones in our library. The data revealed that most of the compounds obey Lipinski’s rule of five, may be absorbed by the gastrointestinal (GI)tract, may not penetrate the blood-brain barrier, and possess drug-like properties. This research data informs both the scientific and non-scientific communities with vital strategies for early drug development.