title: Isoniazid derivatives and their anti-tubercular activity.
abstract: Tuberculosis (TB), which has been a scourge of humanity for thousands of years, is a worldwide pandemic disease caused mainly by Mycobacterium tuberculosis (MTB). The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and totally drug-resistant TB (TDR-TB) increase the challenges to eliminate TB worldwide. Isoniazid (INH), a critical frontline anti-TB drug, is one of the most effective drugs used to treatment of TB infection for more than 60 years. Unfortunately, bacterial strains resistant to INH are becoming common which mainly due to the long-term widely use even abuse. Therefore, there is an urgent need to develop novel anti-TB agents. Numerous efforts have been undertaken to develop new anti-TB agents, but no new drug has been introduced for more than 5 decades. It has been suggested that the incorporation of lipophilic moieties into the framework of INH can increase permeation of the drug into bacterial cells, thereby enhancing the anti-TB. Therefore, INH derivatives with greater lipophilicity are emerging as one of the most potential anti-TB agents. Indeed, the INH derivative LL-3858 is in initial stages of phase II clinical trial for the treatment of TB and may be approved to treat TB in the near future. This review aims to summarize the recent advances made towards the discovery anti-TB agents holding INH as a nucleus including INH hybrids and INH hydrazide-hydrazone derivatives.
authors.affiliation: School of Chemistry and Materials Science, Hubei Engineering University, Hubei, PR China.
authors.forename: Yuan-Qiang
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: Pony Testing International Group (Wuhan), Hubei, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: WuXi AppTec (Wuhan), Hubei, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: WuXi AppTec (Wuhan), Hubei, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Gao
authors.affiliation: WuXi AppTec (Wuhan), Hubei, PR China.
authors.forename: Lian-Shun
authors.initials: LS
authors.lastname: Feng
authors.affiliation: Wuhan University of Science and Technology, Hubei, PR China.
authors.forename: Zao-Sheng
authors.initials: ZS
authors.lastname: Lv
authors.affiliation: WuXi AppTec (Wuhan), Hubei, PR China; Wuhan University of Science and Technology, Hubei, PR China. Electronic address: chemorgchem@126.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: WuXi AppTec (Wuhan), Hubei, PR China. Electronic address: wu_xiang@wuxiapptec.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid
keywords: Anti-mycobacterial activity; Anti-tubercular activity; Hybrid compounds; Hydrazide-hydrazone derivatives; Isoniazid derivatives; Structure-active relationship