Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore, India.
Department of Chemistry, Nowrosjee Wadia College, Pune, India.
Arch Pharm (Weinheim). 2018 May;351(5):e1700325. doi: 10.1002/ardp.201700325. Epub 2018 Apr 3.
Tuberculosis (TB) is a highly dreaded, infectious, chronic, airborne disease affecting more than two million people all around the world, with more than eight million cases every calendar year. TB is the second leading infectious cause of death after HIV/AIDS. Over the past few decades, numerous efforts have been undertaken to develop new anti-TB agents. The current frontline therapy for TB consists of administering three or more different drugs (usually isoniazid, rifampin, pyrazinamide, and ethambutol) over an extended period of time. But these drugs will take 6-12 months to cure TB, along with many side effects; hence, there is an urgent need to explore new anti-TB agents. Quinoxaline derivatives are a class of compounds that show a spectrum of biological properties and the interest in these compounds is exponentially growing within the field of medicinal chemistry. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas. Since quinoxaline derivatives are regarded as a new class of effective anti-TB candidates, their 1,4-di-N-oxide analogues may show promising in vitro and in vivo anti-TB activities and might be able to prevent the drug resistance to a certain extent. Therefore, the main aim of this review is to focus on important quinoxaline and quinoxaline-1,4-di-N-oxide analogues that have shown anti-TB activities, and their structure-activity relationships for designing anti-TB agents with better efficacies. The present review will be helpful in providing insights for rational designs of more active and less toxic quinoxaline-based anti-TB prodrugs.
结核病（TB）是一种高度令人恐惧的、传染性的、慢性的、空气传播疾病，影响着全球两百多万人，每年有超过八百万例病例。结核病是继艾滋病之后第二大致死的传染病。在过去的几十年中，人们已经做出了许多努力来开发新的抗结核药物。目前结核病的一线治疗包括在较长时间内服用三种或更多种不同的药物（通常是异烟肼、利福平、吡嗪酰胺和乙胺丁醇）。但这些药物需要 6-12 个月才能治愈结核病，同时还伴随着许多副作用；因此，迫切需要探索新的抗结核药物。喹喔啉衍生物是一类具有多种生物活性的化合物，在药物化学领域，人们对这些化合物的兴趣正在迅速增长。喹喔啉-1,4-二-N-氧化物衍生物已被证明可以改善生物效果，并且具有抗病毒、抗癌、抗菌和抗原生动物活性，在许多其他治疗领域都有应用。由于喹喔啉衍生物被认为是一类新的有效抗结核候选药物，它们的 1,4-二-N-氧化物类似物可能具有有前途的体外和体内抗结核活性，并可能在一定程度上防止耐药性的产生。因此，本综述的主要目的是关注具有抗结核活性的重要喹喔啉和喹喔啉-1,4-二-N-氧化物类似物，以及它们的构效关系，为设计具有更好疗效的抗结核药物提供思路。本综述将有助于为更有效和毒性更小的基于喹喔啉的抗结核前药的合理设计提供见解。
