Ridahunlang Nongkhlaw, Bisht Rohit, Rishanlang Nongkhlaw
Department of Chemistry, North Eastern Hill University, Shillong, India.
Department of Pharmaceutical Research, Research Communication Lab, Haldwani, Uttarakhand, India.
Infect Disord Drug Targets. 2023;23(3):e041022209552. doi: 10.2174/1871526522666221004152324.
Tuberculosis (TB) is one of the fatal infectious diseases, making it one of the causes of death in the infectious mortality strata, and it is of prime concern globally. It is spread by a causative agent called Mycobacterium tuberculosis (Mtb) which gets ingressed within the host cells. The current clinical interventions have been associated with various limitations, such as a long treatment regimen (6 months), low lipophilicity of drugs to penetrate the bacterial cell, associated side effects and emerging incidence of multiple drug-resistant strains. Despite these limitations, Isoniazid (INH), a first-line agent, remains a drug of choice to date due to its effectiveness. However, INH is associated with poor penetration into the bacteria cell wall and ultimately leads to the low therapeutic distribution of drugs into the lungs.
Studies have shown that the structural modifications of INH by introducing more lipophilic moiety could lead to its better penetration into the bacterial cell wall resulting in better anti-TB activities.
This review updates various studies conducted on INH derivatives as anti-tubercular (Anti-TB) agents, including in silico and preclinical investigations. In addition, updates on clinical investigations of novel anti-TB molecules have also been highlighted.
The article focuses on the structural modification of various INH derivatives reported, including the in vitro studies and molecular modelling preclinical and clinical investigations of various INH derivatives.
结核病是致命的传染病之一，是导致感染性死亡分层中死亡的原因之一，在全球范围内备受关注。它由一种名为结核分枝杆菌（Mtb）的病原体传播，该病原体可侵入宿主细胞。目前的临床干预措施存在各种局限性，例如治疗方案长（6个月）、药物亲脂性低难以穿透细菌细胞、存在相关副作用以及多重耐药菌株的出现。尽管存在这些局限性，但一线药物异烟肼（INH）由于其有效性，至今仍是首选药物。然而，INH难以穿透细菌细胞壁，最终导致药物在肺部的治疗分布较低。
研究表明，通过引入更多亲脂性部分对INH进行结构修饰可使其更好地穿透细菌细胞壁，从而产生更好的抗结核活性。
本综述更新了关于INH衍生物作为抗结核药物的各种研究，包括计算机模拟和临床前研究。此外，还重点介绍了新型抗结核分子的临床研究进展。
本文重点关注所报道的各种INH衍生物的结构修饰，包括各种INH衍生物的体外研究、分子建模、临床前和临床研究。
