Natural aloe emodin-hybridized sulfonamide aminophosphates as novel potential membrane-perturbing and DNA-intercalating agents against Enterococcus faecalis

Deng, Zhao; Sun, Hang; Bheemanaboina, Rammohan R. Yadav; Luo, Yan; Zhou, Cheng‐He

doi:10.1016/j.bmcl.2022.128695

Cited by 23 publications

(6 citation statements)

References 65 publications

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“…To examine the ROS levels of P. aeruginosa 27,853 cells treated by 11f , dichlorofluorescein diacetate (DCFH-DA) was employed as a fluorometric dye. The DCFH-DA probe itself has no fluorescence, but it can be oxidized by ROS into green fluorescent dichlorofluorescein (DCF), and the fluorescence intensity was proportional to ROS levels [ 64 , 65 ]. As seen in Figure 10 , after incubating with increasing concentrations of the molecule 11f , the fluorescence intensity in P. aeruginosa 27,853 escalated and the cells stained with green fluorescence became gradually dense, which validated that coumarin 11f could trigger an endocellular ROS burst.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

et al. 2023

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A class of piperazine hybridized coumarin indolylcyanoenones was exploited as new structural antibacterial frameworks to combat intractable bacterial resistance. Bioactive assessment discovered that 4-chlorobenzyl derivative 11f showed a prominent inhibition on Pseudomonas aeruginosa ATCC 27853 with a low MIC of 1 μg/mL, which was four-fold more effective than norfloxacin. Importantly, the highly active 11f with inconspicuous hemolysis towards human red blood cells displayed quite low proneness to trigger bacterial resistance. Preliminary explorations on its antibacterial behavior disclosed that 11f possessed the ability to destroy bacterial cell membrane, leading to increased permeability of inner and outer membranes, the depolarization and fracture of membrane, and the effusion of intracellular components. Furthermore, bacterial oxidative stress and metabolic turbulence aroused by 11f also accelerated bacterial apoptosis. In particular, 11f could not only effectively inset into DNA, but also bind with DNA gyrase through forming supramolecular complex, thereby affecting the biological function of DNA. The above findings of new piperazine hybridized coumarin indolylcyanoenones provided an inspired possibility for the treatment of resistant bacterial infections.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

et al. 2023

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“…[ 34 ] Damage to the bacterial cell membrane facilitates the entry of drugs into the interior of the bacteria to bind with DNA, resulting in the inhibition of DNA replication. [ 35 ]…”

Section: Resultsmentioning

confidence: 99%

Discovery of Alkaloid Quinazolone‐Derived Imidazolenones with Novel Structural Scaffolds of Multitargeting Antibacterial Potential

Dai,

Battini,

Zang

et al. 2023

Chin. J. Chem.

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Comprehensive SummaryAlkaloids are one of the prominent members in the development of new antimicrobial agents. This work discovered a class of alkaloid quinazolone‐derived imidazolenones as novel structural type of antibacterial agents with large potential to treat severe bacterial infections in the agricultural and food field. Preliminary bioactive assay displayed that some of the prepared compounds exhibited good inhibition against the tested strains, and cyclohexylimidazole‐derived 7‐fluoroquinazolone 22a (MIC = 0.002 mmol/L) exhibited a 12.5‐fold stronger inhibition than norfloxacin against Escherichia coli ATCC 25922. Further studies revealed that compound 22a not only possessed the ability of rapid bactericidal property and low propensity to develop resistance but also showed low cytotoxic effects toward red blood cells. The preliminary mechanism exploration indicated that compound 22a could cause membrane damage by disrupting bacterial membrane as well as depolarizing the cell membrane. Moreover, compound 22a could insert into DNA, which might hinder the replication of DNA. Molecular docking suggested that compound 22a could bind to gyrase and topoisomerase, which might be due to the suppressed expression of related genes. Meanwhile, compound 22a could disorder the metabolism and stimulate the production of reactive oxygen species to affect bacterial growth. The series of investigations suggested the promise of alkaloid quinazolone‐derived imidazolenones as novel multitargeting antibacterial candidates for treatment of bacterial infections.

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“…[4] Much effort is being directed towards the further modification of natural aloe emodin. Our previous work revealed that hybridization of aloe emodin with sulfanilamides displayed promising antibacterial activity through multifaceted synergistic effects, [5] and azolyl hybrids with simple methylene linker showed broad-spectrum antibacterial potential with MIC values ranging from 1 to 64 μg/mL, which suggested large potential for further development as new type of antibacterial agents. [6] Hydrazone contains an unusual Schiff base (-C=N-) unit with a hydrazino fragment (-NHNH2), which plays a positive role in binding with biotargets.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents

Wang,

Deng,

Bibi

et al. 2024

Chin. J. Chem.

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Comprehensive SummaryA type of unique azole‐hybridized acylhydrazonyl aloe emodins (AAEs) were developed as new antibacterial agents for combating bacterial infections. Some target AAEs showed strong antibacterial activities, especially, tetrazolylthioether AAE 27a exhibited broad antibacterial spectrum with 16—256 folds and 8—64 folds more active antibacterial efficacy than the reference drugs aloe emodin and norfloxacin, respectively. Tetrazolylthioether AAE 27a also gave low hemolysis and cytotoxicity, as well as favorable bioavailability. Preliminary mechanism explorations revealed that tetrazolylthioether AAE 27a could cause bacterial membrane depolarization and damage the cell membrane, resulting in nucleic acid leakage. Moreover, compound 27a could intercalate into DNA to impede its replication and form supramolecular 27a‐DNA gyrase complex to disturb the function of DNA gyrase. These findings would provide valuable insights for the further exploration of azolyl acylhydrazonyl aloe emodins as new potential antibacterial candidates.

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Natural aloe emodin-hybridized sulfonamide aminophosphates as novel potential membrane-perturbing and DNA-intercalating agents against Enterococcus faecalis

Cited by 23 publications

References 65 publications

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

Discovery of Alkaloid Quinazolone‐Derived Imidazolenones with Novel Structural Scaffolds of Multitargeting Antibacterial Potential

Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents

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