Identification of benzothiazinones containing an oxime functional moiety as new anti-tuberculosis agents

Wang, Apeng; Lv, Kai; Tao, Zeyu; Gu, Jian; Fu, Ling; Liu, Mingliang; Wan, Baojie; Franzblau, Scott G.; Ma, Chao; Ma, Xican; Han, Bing; Wang, Aoyu; Xu, Shijie; Lu, Yu

doi:10.1016/j.ejmech.2019.111595

Cited by 24 publications

(24 citation statements)

References 20 publications

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“…Benzothiazinones destroy the integrity of the bacterial cell wall by the inhibition of DprE1‐catalyzed conversion of decaprenylphosphoryl‐β‐D‐ribose (DPR) to decaprenylphosphoryl‐β‐D‐arabinose (DPA) [8g] . Inspired by BTZ043 and PBTZ169, a lot of benzothiazinones were synthesized and biologically evaluated against tuberculosis, most of which showed potent antitubercular activity [8a–d,f, i, j,9,11] . However, the structural modification of these benzothiazinones were focused on the C‐2 position of the scaffold.…”

Section: Introductionmentioning

confidence: 99%

Molecular Insight into the Discrepancy of Antitubercular Activity between 8‐Nitro and 8‐Cyano Benzothiazinones

et al. 2020

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Benzothiazinones with 8-NO 2 group is a novel class of compounds with potent antitubercular activity, especially BTZ043 and PBTZ169, which covalently inhibit DprE1. 8-CN benzothiazinones is reported as another type of benzothiazinones with potent antitubercular activity. Taking this as the starting point, a series of 8-CN benzothiazinones are synthesized and evaluated for their antitubercular activity. To better understand the antitubercular activity of this series of benzothiazinones, the difference between the molecular structures of CN01 and PBTZ169 in crystal are analyzed. CN01 and PBTZ169 show completely different conformations of the piperazine ring. Density functional theory analysis (DFT) and molecular dynamics (MD) simulation are performed to provide more details to explain the different antitubercular activity. All the analysis based on crystallography, quantum chemistry, and molecular modeling lay a foundation for the subsequent structural optimization of 8-CN benzothiazinones.

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Section: Introductionmentioning

confidence: 99%

Molecular Insight into the Discrepancy of Antitubercular Activity between 8‐Nitro and 8‐Cyano Benzothiazinones

et al. 2020

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“…[ 13 ] As such, many approaches to develop new anti‐TB agents via hybridization of TB drugs with NO‐releasing moieties were developed (Figure 1). [ 15–20 ]…”

Section: Introductionmentioning

confidence: 99%

“…[13] As such, many approaches to develop new anti-TB agents via hybridization of TB drugs with NO-releasing moieties were developed (Figure 1). [15][16][17][18][19][20] Given the aforementioned reports, we herein examine the im- was carried out to study the impact of the introduced substitutions at the piperazinyl N-4 nitrogen on the overall binding with DNA gyrase.…”

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confidence: 99%

Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids

Aziz

Moustafa

Abuo‐Rahma

et al. 2020

Archiv der Pharmazie

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The contents of this page will be used as part of the graphical abstract of html only. It will not be published as part of main. A new series of nitric oxide-donating fluoroquinolone/oximes was prepared in this study. Evaluation of their antitubercular activity revealed that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. More important, oximes 3c-e are highly potent against Klebsiella pneumoniae, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin.

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“…The oxime and oxime ether moiety are privileged groups in medicinal chemistry due to its presence in a large number of medicinal scaffolds that exhibit a broad range of biological and pharmaceutical activities, including anticancer, [8][9][10][11][12][13][14] antiinflammatory, [15][16][17] antibacterial, [18][19] antiviral, [20][21][22] antituberculosis, [23][24] and antimicrobial [25][26][27] activities. Steroidal oximes and their derivatives are known to exhibit remarkable anticancer and anti-inflammatory activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Uscharin Oxime Analogues and Their Biological Evaluation as HIF‐1 Inhibitors

et al. 2020

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Uscharin-like non-classical cardenolides are considered to be useful as HIF-1 inhibitors in the treatment of cancers. To develop more potent HIF-1 inhibitors, oximes and oxime ethers of uscharin were designed and synthesized. Oximation of uscharin exhibited unexpectedly a regioselectivity and stereoselectivity at 3'-thiazoline but not at the 19-aldehyde group, since either E-ketoxime derivative 2 or its ether 5 at C-3' was found as the only product during oximation of uscharin using hydroxylamine or methoxyamine at room temperature. Two 19-aldoxime derivatives 4 and 6 were also synthesized. Ketoxime analogue 2 showed more potent inhibitory effect on HIF-1 transcriptional activity than the parental uscharin. Ketoxime ether 5 and 19-aldoxime 6 exhibited stronger HIF-1 suppressing effect than digoxin (the positive control drug). Moreover, ketoxime derivative 2 displayed the most potent anti-proliferative activity against MCF-7 cancer cells among all compounds. An analysis of structure-activity relationship revealed that 3'-ketoxime is a superior moiety to a thiazoline ring, while 19-aldoxime is inferior to an aldehyde counterpart. Our findings may provide some guidance for the rational design of uscharin-based promising HIF-1 inhibitors.

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Identification of benzothiazinones containing an oxime functional moiety as new anti-tuberculosis agents

Cited by 24 publications

References 20 publications

Molecular Insight into the Discrepancy of Antitubercular Activity between 8‐Nitro and 8‐Cyano Benzothiazinones

Molecular Insight into the Discrepancy of Antitubercular Activity between 8‐Nitro and 8‐Cyano Benzothiazinones

Synthesis and antimicrobial evaluation of new nitric oxide‐donating fluoroquinolone/oxime hybrids

Synthesis of Uscharin Oxime Analogues and Their Biological Evaluation as HIF‐1 Inhibitors

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