Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase

Líu, Hao; Chu, Zhiwen; Xia, Dong-Guo; Cao, Haiqun; Lv, Xian-Hai

doi:10.1016/j.bioorg.2020.103807

Cited by 36 publications

(11 citation statements)

References 30 publications

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“…Therefore, these compounds possess other molecular mechanisms of action. Possibly, compound 4 , with high antibacterial activity, should be investigated for inhibitory activity toward S. aureus DNA gyrase, since according to recent literature data, several indole derivatives demonstrate antistaphylococcal activity targeting this enzyme [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A

et al. 2021

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Staphylococcus aureus (S. aureus) is a causative agent of many hospital- and community-acquired infections with the tendency to develop resistance to all known antibiotics. Therefore, the development of novel antistaphylococcal agents is of urgent need. Sortase A is considered a promising molecular target for the development of antistaphylococcal agents. The main aim of this study was to identify novel sortase A inhibitors. In order to find novel antistaphylococcal agents, we performed phenotypic screening of a library containing 15512 compounds against S. aureus ATCC43300. The molecular docking of hits was performed using the DOCK program and 10 compounds were selected for in vitro enzymatic activity inhibition assay. Two inhibitors were identified, N,N-diethyl-N′-(5-nitro-2-(quinazolin-2-yl)phenyl)propane-1,3-diamine (1) and acridin-9-yl-(1H-benzoimidazol-5-yl)-amine (2), which decrease sortase A activity with IC50 values of 160.3 µM and 207.01 µM, respectively. It was found that compounds 1 and 2 possess antibacterial activity toward 29 tested multidrug resistant S. aureus strains with MIC values ranging from 78.12 to 312.5 mg/L. These compounds can be used for further structural optimization and biological research.

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Section: Resultsmentioning

confidence: 99%

Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A

et al. 2021

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“…TLC 3:1 n-hexane: ethyl acetate indicates the end of the reaction in about 10-12 hours. The mono-substituted indole precipitate after reducing solvent, filtered, washed, and dried (20)(21)(22). Two derivatives were synthesized in this step: 2) (0.15 g, 0.00035 mmol) was coupled with 2-deoxy-2-amino-D-glucose according to general procedure mentioned in step-1 above to yield yellow crystals of (2S,3S,4R,5S)-2- and S3).…”

Section: Tools and Instrumentsmentioning

confidence: 99%

New Bioactive Aromatic Heterocyclic Macromolecules with Monosaccharide Core

MAHMOOD¹,

Salman

ABD

2022

Journal of the Turkish Chemical Society Section A: Chemistry

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1,1,2-trimethyl-1H-benzo[e]indole is an important heterocyclic compound, its available in reasonable price and can easily modified to make a good intermediate for other derivatives. That is quite enough reasons to use as starting material for a new series of compounds with other biomolecules such as monosaccharides after simple modification. The target molecules show biological activity. So, the current work is aiming to improve the activity and the properties of the benzo indole by attaching with a naturally occurring, and biodegradable compounds represented by 2-deoxy-2-amino -d-glucose and 6-deoxy-6-amino-d-glucose to synthesis both mono and di-saccharides derivatives of benzo indole. Two steps synthesis were used for mono-saccharide derivatives and three steps for di-saccharide derivatives, the first is the functionalization of 1,1,2-trimethyl-1H-benzo[e]indole [1] via the reaction with POCl3 to produce 2-(1,1-dimethyl-1H-benzo[e]indol-2(3H)-ylidene) malonaldehyde [2] with two aldehydes reaction centers, while in the second step the latter was coupled with sugar via amino groups to get the two monosaccharide derivatives [3,5], while the disaccharides molecules [4,6] taken one more step with harder conditions to overcome the steric hindrance at the other reaction center. The purity and characterization of the target molecules was confirmed using spectroscopy methods including 1H NMR and 13 NMR. The synthesized compound shows a good biological activity as antibacterial antifungal.

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“…1). 44,45 More particularly, pyrazole–thiophene derivatives G , 46 pyrazole-Schiff bases H , 47 and pyrazole–piperidine derivatives I 48 exemplify the same as potent antibacterial agents. Similarly, many reported scaffolds with a urea moiety do act as potent DNA gyrase inhibitors embodied with antibacterial properties.…”

Section: Introductionmentioning

confidence: 99%