title: Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents.
abstract: A series of quinoxaline 1,4-di-N-oxide derivatives variously substituted at C-2 position were synthesized and evaluated for in vitro antimycobacterial activity. Seventeen compounds exhibited potential activity (MIC ⩽6.25μg/mL) against Mycobacterium tuberculosis (H37Rv), in particular the compounds 3d and 3j having an MIC value of 0.39μg/mL. None of the compounds exhibited cytotoxicity when using an MTT assay in VERO cells. To further investigate the structure-activity relationship, CoMFA (q(2)=0.507, r(2)=0.923) and CoMSIA (q(2)=0.665, r(2)=0.977) models were performed on the basis of antimycobacterial activity data. The 3D-QSAR study of these compounds can provide useful information for further rational design of novel quinoxaline 1,4-di-N-oxides for treatment of tuberculosis.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Li
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xie
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Menghong
authors.initials: M
authors.lastname: Dai
authors.affiliation: MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hao
authors.affiliation: MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.affiliation: MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Liye
authors.initials: L
authors.lastname: Wang
authors.affiliation: MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Assessment of Quality and Safety of Livestock and Pourtry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010087:Oxides / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D010087:Oxides; D011810:Quinoxalines
keywords: 3D-QSAR; Antimycobacterial activity; CoMFA; CoMSIA; Quinoxaline 1,4-di-N-oxide; Tuberculosis