Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies

Hassan, Nayera W.; Saudi, M. N. S.; Abdel‐Ghany, Yasser S.; Ismail, Azza; Elzahhar, Perihan A.; Sriram, Dharmarajan; Nassra, Rasha A.; Abdel‐Aziz, Marwa M.; El-Hawash, Soad A.M.

doi:10.1016/j.bioorg.2020.103610

Cited by 46 publications

(26 citation statements)

References 76 publications

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“…The molecular docking study of these compounds in the active site of the PS enzyme demonstrated favourable binding modes and interaction pattern. 57 Overall, in this manuscript, seven different methods used for the identication of potential PS inhibitors reported by various scientists across the globe have been systematically compiled, and we observe the following SAR pattern:…”

Section: Molecular Hybridization-based Ps Inhibitorsmentioning

confidence: 88%

Inhibitors of pantothenate synthetase ofMycobacterium tuberculosis– a medicinal chemist perspective

et al. 2020

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Section: Molecular Hybridization-based Ps Inhibitorsmentioning

confidence: 88%

Inhibitors of pantothenate synthetase ofMycobacterium tuberculosis– a medicinal chemist perspective

et al. 2020

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“…On the other hand, 13 C NMR spectra for hybrids 5a-m and 9a-c showed two signals resonating in the range d 32 . INH was used as the reference drug.…”

Section: Chemistrymentioning

confidence: 92%

“…The anti-tubercular activity against Isoniazid and Streptomycin resistant M. tuberculosis (ATCC 35823) was evaluated using MABA 32 . Investigating the results of the target compounds 5a-m, 9a-c, and 14 (Table 1), it was found that many of the tested derivatives exhibited potent to moderate activity with MIC range ¼ 3.9-62.5 mg/mL.…”

Section: Anti-tubercular Activity Towards Isoniazid and Streptomycin mentioning

confidence: 99%

“…Microplate Alamar blue assay (MABA) 32 has been utilised to determine MICs for all herein prepared hybrids (5a-m, 9a-c, and 14) against M. tuberculosis ATCC 27294 (Isoniazid-susceptible strain) and Mycobacterium tuberculosis ATCC 35823 (Isoniazid and Streptomycin resistant strain). The detailed procedures were presented in the supporting materials.…”

Section: Anti-tubercular Activitymentioning

confidence: 99%

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Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistantMycobacterium tuberculosisand bronchitis causing–bacteria

Elsayed

Eldehna

Abdel‐Aziz

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Several inhibitors that target MtPanC have been identified through various screening methods (White et al, 2007;Velaparthi et al, 2008;Yang et al, 2011;Kumar et al, 2013;Ntie-Kang et al, 2013;Samala et al, 2013;Naidu et al, 2014;Samala et al, 2014;Naidu et al, 2016;Naidu et al, 2016;Amaroju et al, 2017;Pradhan and Sinha, 2018;Kumar et al, 2019;Hassan et al, 2020;Singireddi et al, 2020). White et al (2007) developed an automated high-throughput screen (HTS) by adapting the coupled assay first used by Zheng and Blanchard (2001), and used it to identify known drugs that inhibit MtPanC.…”

Section: Panc Inhibitors Identified By Screeningmentioning

confidence: 99%

Vitamin in the Crosshairs: Targeting Pantothenate and Coenzyme A Biosynthesis for New Antituberculosis Agents

Butman

Kotze

Dowd

et al. 2020

Front. Cell. Infect. Microbiol.

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Despite decades of dedicated research, there remains a dire need for new drugs against tuberculosis (TB). Current therapies are generations old and problematic. Resistance to these existing therapies results in an ever-increasing burden of patients with disease that is difficult or impossible to treat. Novel chemical entities with new mechanisms of action are therefore earnestly required. The biosynthesis of coenzyme A (CoA) has long been known to be essential in Mycobacterium tuberculosis (Mtb), the causative agent of TB. The pathway has been genetically validated by seminal studies in vitro and in vivo. In Mtb, the CoA biosynthetic pathway is comprised of nine enzymes: four to synthesize pantothenate (Pan) from l-aspartate and α-ketoisovalerate; five to synthesize CoA from Pan and pantetheine (PantSH). This review gathers literature reports on the structure/mechanism, inhibitors, and vulnerability of each enzyme in the CoA pathway. In addition to traditional inhibition of a single enzyme, the CoA pathway offers an antimetabolite strategy as a promising alternative. In this review, we provide our assessment of what appear to be the best targets, and, thus, which CoA pathway enzymes present the best opportunities for antitubercular drug discovery moving forward.

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Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies

Cited by 46 publications

References 76 publications

Inhibitors of pantothenate synthetase ofMycobacterium tuberculosis– a medicinal chemist perspective

Inhibitors of pantothenate synthetase ofMycobacterium tuberculosis– a medicinal chemist perspective

Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistantMycobacterium tuberculosisand bronchitis causing–bacteria

Vitamin in the Crosshairs: Targeting Pantothenate and Coenzyme A Biosynthesis for New Antituberculosis Agents

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