Quinoline Derivatives with Potential Activity Against Multidrug‐resistant Tuberculosis

Abstract

Tuberculosis (TB), which affects primarily the lungs (pulmonary TB) apart from other vital organs, is a life‐threatening chronic deadliest infectious disease caused by members of Mycobacterium tuberculosis (MTB) complex and mainly by MTB itself. The emergence of MTB new virulent forms that are resistant to some or all first‐line and second‐line anti‐TB agents, including multidrug‐resistant (MDR), extensively drug‐resistant, and totally drug‐resistant strains has further aggravated the spread of this disease and was increased up to an alarming level in the recent decades. More than ever, it is imperative to develop novel, high effective, and fast acting anti‐TB drugs to prevent the spread of TB, particularly in its hard‐to‐kill MDR‐TB, extensively drug‐resistant‐TB, and totally drug‐resistant‐TB strains. In recent years, numerous compounds have been synthesized for this purpose, but only a handful of compounds have entered human trials after the discovery of rifampicin, reflecting the inherent difficulties of developing new anti‐TB agents. Despite of bedaquiline and delamanid have received approval from many countries for treatment of MDR‐TB infected patients, both drugs are associated with serious side effects and are only recommended for those MDR‐TB patients without other treatment options. All these aforementioned facts make it an urgent need to develop novel drugs. Quinoline‐based derivatives including quinolones ex biological activities, and some of them displayed excellent in vitro and in vivo activities against MDR‐TB. This review outlines the recent developments of quinoline‐based derivatives with potential activity against MDR‐TB as well as the structure–activity relationship.

Preparation, carbonic anhydrase enzyme inhibition and antioxidant activity of novel 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives incorporating mono or dipeptide moiety

“…2-Quinolinones derivatives constitute a privilege class of heterocyclic compounds for their wide range of important biological properties such as such as antibacterial 1,2 , antimalarial 3 , antitumor 4 , carbonic anhydrase inhibitor 5,6 , antioxidant, anti-tuberculosis 7 , antiparasitic 8 and anti-hepatit C and B viruses activity 9 . For example, the 3,4-dihydro-2-quinolinone structure is found in a number of biologically active and FDA approved medicine such as cilostazol, carteolol and aripiprazole.…”

Ciprofloxacin–Isatin Hybrids and Their Antimycobacterial Activities

“…The first‐line anti‐TB agents such as isoniazid ( INH ), rifampicin ( RIF ), pyrazinamide, and ethambutol are still crucial therapeutics for the treatment of drug‐susceptible MTB‐infected patients . However, the evolution of MTB new virulent forms such as drug‐resistant TB, multidrug‐resistant TB (MDR‐TB), and extremely drug‐resistant TB as well as MTB co‐infection with HIV has created a global epidemic problem . Thus, there is an urgent need to develop novel, fast‐acting, and more effective anti‐TB drugs.…”

“…Fluoroquinolones are emerged as a family of synthetic broad spectrum antibiotics with extensive indications for infections, and some fuloroquinolones demonstrated excellent in vitro and in vivo anti‐TB activity . Furthermore, MTB isolates expressing resistance to both INH and RIF are sensitive to fluoroquinlones generally .…”

Design, Synthesis, and Evaluation of Tetraethylene Glycol Tethered Ciprofloxacin–Isatin Hybrids as Novel Antitubercular Agents

“…Moreover, CPFX has been recommended as the second‐line anti‐TB agents by the World Health Organization for the treatment of TB mainly in cases involving resistance or intolerance to first‐line anti‐TB therapy . Various CPFX derivatives have been synthesized in order to improve the anti‐TB activity, and some of them possess excellent in vitro and in vivo activity against both drug‐sensitive and MDR MTB strains .…”