title: Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.
abstract: 5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy.
authors.affiliation: School of Food Science and Biotechnology, Zhejiang Gongshang University, 18 Xuezheng Street, Xiasha, Hangzhou, Zhejiang 310018, PR China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhu
authors.affiliation: Biological Sciences Department, University of Essex, Wivenhoe Park CO4 3SQ, United kingdom.
authors.forename: Sinan
authors.initials: S
authors.lastname: Battah
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Kong
authors.affiliation: Biological Sciences Department, University of Essex, Wivenhoe Park CO4 3SQ, United kingdom.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Reeder
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.affiliation: School of Food Science and Biotechnology, Zhejiang Gongshang University, 18 Xuezheng Street, Xiasha, Hangzhou, Zhejiang 310018, PR China. Electronic address: taozhou@zjgsu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005260:Female; D006801:Humans; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D011728:Pyridones / Q000737:chemistry*
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D011728:Pyridones; D000622:Aminolevulinic Acid
keywords: 5-Aminolaevulinic acid; Hydroxypyridinone; Iron chelators; Photodynamic therapy; Protoporphyrin IX