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

• 作者: Fidelis Toloyi Ndombera Geoffrey K.K.Maiyoh Vivian C.Tuei
• 来源期刊: 药剂与药理学:英文版
• 学科: 医学
• 关键词: ANTICANCER agent N-glycoside 2-deoxy-D-glucose pharmacokinetics lung cancer
• 年，卷（期）: 2019,（4）
• 页码范围: 165-176
• 页数: 12页
• 分类号: R

摘要

Acetylated N-xyloside of 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.