Easily accessed nitroquinolones exhibiting potent and selective anti-tubercular activity

Dube, Phelelisiwe S.; Legoabe, Lesetja J.; Jordaan, Audrey; Jesumoroti, Omobolanle J.; Tshiwawa, Tendamudzimu; Warner, Digby F.; Beteck, Richard M.

doi:10.1016/j.ejmech.2021.113207

Cited by 9 publications

(15 citation statements)

References 30 publications

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“…The antitubercular activity reported as minimum inhibitory concentration (MIC) was determined by the standard broth microdilution method following the procedure reported by Dube et al (2021). Briefly, a 10 ml culture of M.tb pMSp12::GFP was grown to an optical density (OD600) of 0.6–0.7, in a Middlebrook 7H9 medium supplemented with either 0.03% casitone, 0.4% glucose, and 0.05% tyloxapol, or 0.03% albumine, 0.4% glucose, and 0.05% tween 80.…”

Section: Methodsmentioning

confidence: 99%

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Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

et al. 2022

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Curcumin is a natural product that has been reported to exhibit myriad pharmacological properties, one of which is antitubercular activity. It demonstrates antitubercular activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses that ultimately lead to the elimination of M.tb by macrophages. This natural product is, however, unstable, and several analogues, noticeably monocarbonyl analogues, have been synthesized to overcome this challenge. Curcumin and its monocarbonyl analogues reported so far exhibit moderate antitubercular activity in the range of 7 to 16 μM. Herein, we report a straightforward synthesis of novel monocarbonyl curcumin analogues, their antitubercular activity, and the structure-activity relationship. The hit compound from this study, 3a, exhibits potent MIC 90 values in the range of 0.2 to 0.9 μM in both ADC and CAS media.

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Section: Methodsmentioning

confidence: 99%

“…Relative fluorescence (excitation 485 nM; emission 520 nM) was measured at Day 7 and Day 14 and analyzed to generate MIC 90 values. Rifampicin at 2 × MIC and 5% DMSO were used as the assay minimum and maximum growth controls, respectively (Dube et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

et al. 2022

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“…In vitro antitubercular activity was evaluated essentially as described by Dube et al (2021) [ 42 ]. A 10 mL culture of the test organism, Mtb pMSp12: GFP, was grown on a Middlebrook 7H9 enriched with 0.03% casitone, 0.4% glucose, and 0.05% tyloxapol, to an optical density (0D600) of 0.6–0.7.…”

Section: Methodsmentioning

confidence: 99%

Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents

et al. 2022

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Tuberculosis (TB) is one of the leading causes of death worldwide. Developing new anti-TB compounds using cost-effective processes is critical to reduce TB incidence and accomplish the End TB Strategy milestone. Herein, we describe the synthesis and structure–activity relationships of a library of thirty 7H -Pyrrolo[2,3- d ]pyrimidine derivatives providing insights into the contributions of different aromatic, aryl and alkyl substitution at the C-4 position of the 7-deazapurine ring. The minimum inhibitory concentration (MIC) of the compounds against the green fluorescent protein (GFP) reporter strain of Mycobacterium tuberculosis was assayed using the standard broth microdilution method, and cell toxicity was determined using the MTT assay. Sixteen compounds displayed in vitro activity against the GFP reporter strain of Mycobacterium tuberculosis with MIC 90 values of 0.488–62.5 µM. This study highlights the most potent derivative, N-(4-phenoxy phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine with a MIC 90 value of 0.488 µM and was non-cytotoxic to the Vero cell line. Moreover, all the potent compounds from this series have a ClogP value less than 4 and molecular weight < 400; thus, likely to maintain drug-likeness during lead optimisation. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10453-1.

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“…Although TB is a prehistoric disease, it continues to pose as a global public health threat. TB is currently among the top 10 causes of death and the second leading cause of death from a single pathogenic agent, second only to COVID-19 [ 51 , 52 ]. The greatest impact on TB associated fatalities was projected in 2021 wherein the number of deaths is on par with 2017 records, while the greatest impact on tuberculosis incidence is expected in 2022 [ 52 ].…”

Section: Therapeutic Applications Of Quinolone Containing Compoundsmentioning

confidence: 99%

“…All target compounds were evaluated in vitro for anti-TB activity using the gfp reporter strain of Mtb and twelve compounds exhibiting antitubercular activity in the range of < 0.244–31.865 µM were identified. The hit compound ( 67 ) had a MIC 90 of < 0.244 µM and docking studies showed that this compound binds to DprE1 active site, with its nitro group in proximity with Cys 387 residue [ 51 ].…”

Section: Therapeutic Applications Of Quinolone Containing Compoundsmentioning

confidence: 99%

Quinolone: a versatile therapeutic compound class

2022

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The discovery of nalidixic acid is one pinnacle in medicinal chemistry, which opened a new area of research that has led to the discovery of several life-saving antimicrobial agents (generally referred to as fluoroquinolones) for over decades. Although fluoroquinolones are frequently encountered in the literature, the utility of quinolone compounds extends far beyond the applications of fluoroquinolones. Quinolone-based compounds have been reported for activity against malaria, tuberculosis, fungal and helminth infections, etc. Hence, the quinolone scaffold is of great interest to several researchers in diverse disciplines. This article highlights the versatility of the quinolone pharmacophore as a therapeutic agent beyond the fluoroquinolone profile. Graphical abstract

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Easily accessed nitroquinolones exhibiting potent and selective anti-tubercular activity

Cited by 9 publications

References 30 publications

Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents

Quinolone: a versatile therapeutic compound class

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