title: Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4-Hydroxyproline.
abstract: A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L).
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. llxx.love@163.com.
authors.forename: Guorui
authors.initials: G
authors.lastname: Cao
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. yk060606@126.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. a4931778@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. routechem@163.com.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. routechem@163.com.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. dteng@qust.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Teng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D061565:Cycloaddition Reaction; D056945:Hep G2 Cells; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D002945:Cisplatin; D006909:Hydroxyproline
keywords: 4-hydroxyproline; Mitsunobu reaction; amide formation; anti-tumor activity; azide-alkyne cycloaddition; macrocycle