Design, synthesis, and biological evaluation of dihydroartemisinin–fluoroquinolone conjugates as a novel type of potential antitubercular agents

Zhou, Fu-Wei; Lei, Huangshu; Fan, Li; Liu, Jian; Peng, Xin-Mei; Xu, Xiaoli; Chen, Li; Zhou, Changtai; Zou, Yan-Ye; Liu, Caiping; Zhi-qin, HE; Yang, Da‐Cheng

doi:10.1016/j.bmcl.2014.03.010

Cited by 43 publications

(16 citation statements)

References 31 publications

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“…However, in spite of their new pharmacological activities/actions provided through these studies, their anti-tuberculosis effects have not yet been reported or studied. Recently it was reported that compounds such as dihydroartemisinin-fluoroquinolone, synthesized using both artemisinin and fluoroquinolone, induced selective anti-tuberculosis activity [45]. …”

Section: Discussionmentioning

confidence: 99%

Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents

Choi

2017

JCM

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Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests. Artesunate showed selective anti-Mtb effects by strongly inhibiting the growth of Mtb compared to artemisinin, and consistently induced anti-Mtb activity/effects by effectively inhibiting Mtb in the MGIT 960 system and in Ogawa slant medium for 21 days with a single dose; its minimum inhibitory concentration was 300 µg/mL in in vitro testing. Furthermore, artesunate demonstrated an anti-tubercular effect/action with a daily dose of 3.5 mg/kg in an in vivo test for four weeks, which did not indicate or induce toxicity and side effects. These results demonstrate that artesunate effectively inhibits the growth and/or proliferation of Mtb through novel pharmacological activities/actions, as well as induces anti-Mtb activity. This study shows its potential as a potent candidate agent for developing new anti-tuberculosis drugs of an effective/safe next generation, and suggests novel insights into its effective use by repurposing existing drugs through new pharmacological activity/effects as one of the substantive alternatives for inhibiting tuberculosis.

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Section: Discussionmentioning

confidence: 99%

Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents

Choi

2017

JCM

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“…The majority of the newly synthesized conjugates 65 – 67 were active and selective against Mycobacterium tuberculosis . Clinafloxacin derivatives 66 and 67 (R = cyclopropyl, X = Cl, Y = pyrrolidin-3-amine) exhibited stronger activity than the parent drug and were extremely potent against reference strain as well as clinical isolates, both sensitive and multidrug resistant [148] (Fig. 18).…”

Section: Hybrid Drugsmentioning

confidence: 99%

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Fedorowicz

Sączewski

2018

Monatsh Chem

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This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.Graphical abstract

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“…Recently, an artemisinin‐fluoroquinolone antibiotic conjugate (Fig. b) was reported to have potent antimycobacterial activity . Among the analogues tested, the authors find that a short linker between the two drugs helped improve antimycobacterial activity.…”

Section: Introductionmentioning

confidence: 99%

Redox‐guided small molecule antimycobacterials

2018

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The emergence of drug resistance has posed a major challenge to treatment of tuberculosis worldwide. The new drug candidates in the pipeline are few and therefore there is an urgent need to develop antimycobacterials with novel mechanisms of action. Maintenance of redox homeostasis is integral to mycobacterial survival and growth. Therefore, perturbation of this equilibrium can result in irreversible stress induction and inhibition of growth. Herein, we review a number of small molecules that have either been designed to induce redox stress or were found to do so after their discovery. A number of these small molecules are quite effective against drug-resistant mycobacterial strains and thus offer scope for exploration of potentially new mechanism of action. The progress in redox-guided antimycobacterial compounds and the challenges towards clinical applications are reviewed. © 2018 IUBMB Life, 70(9):826-835, 2018.

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Design, synthesis, and biological evaluation of dihydroartemisinin–fluoroquinolone conjugates as a novel type of potential antitubercular agents

Cited by 43 publications

References 31 publications

Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents

Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Redox‐guided small molecule antimycobacterials

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