Pharmacokinetic, Physicochemical and Medicinal Properties of N-glycoside Anti-cancer Agent More Potent than 2-Deoxy-D-Glucose in Lung Cancer Cells

Abstract

Acetylated N-xylosideof 1-naphthylamine (K8A) has been shown to be more potent than 2-deoxy-D-glucose in lung cancer cells and has therapeutic potential for further drug development. In this paper we evaluate and report cytotoxicity, pharmacokinetic, physicochemical and medicinal properties of this D-Xylose derivative (K8A) as a lead anticancer agent with greater therapeutic potential than 2-deoxy-D-glucose (2-DG). 2-DG has been in clinical trials for treatment of solid tumors and other types of cancer. We demonstrate using virtual tools that K8A has better “drug-likeness” than 2-DG and does not violate any Lipinski, Ghose, Veber, Egan or Muegge rules. On the other hand, 2-DG violates Ghose and Muegge rules. A “BOILEDegg evaluation”, predicts that K8A has higher gastrointestinal absorption (HIA) than 2-DG and is not effluxed by P-glycoprotein (P-gp). Additionally, K8A does not penetrate the blood brain barrier (BBB) and is not a substrate of most Cytochrome P450 (CYP) enzymes. Importantly, K8A did not show false positive alert from PAINS screening enabling us to narrow down and rule out false targets. Importantly, K8A is more potent than 2-DG in H1299 and A549 lung cancer cells