title: Design, synthesis and evaluation of novel molecules with a diphenyl ether nucleus as potential antitubercular agents.
abstract: A series of compounds with a diphenyl ether nucleus were synthesized by incorporating various amines into the diphenyl ether scaffold with an amide bond. Their antitubercular activities were evaluated against Mycobacterium tuberculosis H(37)Rv by a microdilution method, with MIC values ranging from 4 to 64μg/mL. Through structure-activity relationship studies, the two chlorine atoms at 3 and 4 positions in the phenyl ring of R(2) group were found to play a significant role in the antitubercular activity. The most potent compound 6c showed an MIC value of 4μg/mL and a good safety profile in HepG2 cell line by the MTT assay. Compound 6c was further found to be effective in a murine model of BCG infection, providing a good lead for subsequent optimization.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Wang
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Weiyi
authors.initials: W
authors.lastname: Pi
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.forename: Yanni
authors.initials: Y
authors.lastname: Lin
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zicheng
authors.initials: Z
authors.lastname: Li
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009164:Mycobacterium Infections / Q000188:drug therapy*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000995:Antitubercular Agents; D010647:Phenyl Ethers; C031538:phenyl ether