Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms

Soliman, Sameh S. M.; Saeed, Balsam Qubais; Elseginy, Samia A.; Al-Marzooq, Farah; Ahmady, Islam M.; El‐Keblawy, Ali; Hamdy, Rania

doi:10.1016/j.cbi.2020.109318

Cited by 17 publications

(11 citation statements)

References 40 publications

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“…24 The ethyl acetate fraction also detected an unsaturated aliphatic aldehyde compound is decanal. Based on Soliman, S.S., et al 25 decanal is an antibacterial agent. Decanal compounds have a mechanism of action due to aldehyde groups which are very likely to cause the function of cell membrane proteins, thereby increasing their permeability.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity and Active Fraction of Zingiber officinale Roscoe, Zingiber montanum (J.Koenig) Link ex A., and Zingiber zerumbet (L.) Roscoe ex Sm. Against Propionibacterium acnes

Aji¹,

Kumala²,

Mumpuni³

et al. 2022

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MATERIALS AND METHODS MaterialsThe plant material used was taken from Ciamis Regency, West Java Province, Indonesia. Crops were harvested on March 24, 2021 and then determined. Voucher specimens are stored at the Bandungense Herbarium, Bandung Institute of Technology, with registration numbers: Zingiber officinale Roscoe namely FIPIA-DEP30, Zingiber montanum (J.Koenig) Link ex A., namely FIPIA-DEP29 and Zingiber zerumbet (L.) Roscoe ex Sm. , namely FIPIA-DEP27. The bacteria used were Propionibacterium acne ATCC 11827, the culture medium was Nutrien Agar (Oxoid), and dimethyl sulfoxide /DMSO 99,9 % (Merck) as extract solvent. The materials used in the extraction process are ethanol 70%, the materials used for fractionation are methanol, ethylacetate 99.8% (Satyam), n-hexane 99.9% (Alfa), and aquadestylates (Brataco). Materials used for TLC: Silica Gel 60 F254 (Merck) was used in stationary phase with methanol (Merck) as mobile phase, and

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Section: Discussionmentioning

confidence: 99%

Antibacterial Activity and Active Fraction of Zingiber officinale Roscoe, Zingiber montanum (J.Koenig) Link ex A., and Zingiber zerumbet (L.) Roscoe ex Sm. Against Propionibacterium acnes

Aji¹,

Kumala²,

Mumpuni³

et al. 2022

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“…The cytotoxic activities of flavonoids were assessed blindly using MTT (3-[4, 5-dimethylthiazolyl-2]-2, 5-diphenyltetrazolium bromide) assay according to Soliman, Alhamidi, et al (2020) and Soliman, Saeed, et al (2020). Briefly, in 96-well plates, normal human fibroblast cell line (HDF, passage #6, 106-05A, Sigma-Aldrich) were seeded at 4000 cells/50 μl and incubated for 24 h at 37 C, and 5% CO 2 with the compounds at different concentrations.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS‐CoV‐2

Hamdy

Mostafa

Shama

et al. 2022

Phytotherapy Research

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Flavonoids are phenolic compounds naturally found in plants and commonly consumed in diets. Herein, flavonoids were sequentially evaluated by a comparative in silico study associated with systematic literature search. This was followed by an in vitro study and enzyme inhibition assays against vital SARS‐CoV‐2 proteins including spike (S) protein, main protease (Mpro), RNA‐dependent RNA‐polymerase (RdRp), and human transmembrane serine protease (TMPRSS2). The results obtained revealed 10 flavonoids with potential antiviral activity. Out of them, silibinin showed promising selectivity index against SARS‐CoV‐2 in vitro. Screening against S protein discloses the highest inhibition activity of silibinin. Mapping the activity of silibinin indicated its excellent binding inhibition activity against SARS‐CoV‐2 S protein, Mpro and RdRP at IC50 0.029, 0.021, and 0.042 μM, respectively, while it showed no inhibition activity against TMPRSS2 at its IC50(SARS‐CoV‐2). Silibinin was tested safe on human mammalian cells at >7‐fold its IC50(SARS‐CoV‐2). Additionally, silibinin exhibited >90% virucidal activity at 0.031 μM. Comparative molecular docking (MD) showed that silibinin possesses the highest binding affinity to S protein and RdRP at −7.78 and −7.15 kcal/mol, respectively. MDs showed that silibinin exhibited stable interaction with key amino acids of SARS‐CoV‐2 targets. Collectively, silibinin, an FDA‐approved drug, can significantly interfere with SARS‐CoV‐2 entry and replication through multi‐targeting activity.

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“…The cytotoxic activity was performed using MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5diphenyltetrazolium bromide) assay according to Soliman et al (2020) [80,81]. In 96-well plates, normal human dermal fibroblast cell line (HDF, 106-05A, Sigma, EU) were seeded at 4000 cells/100 µL and incubated with the tested compounds for 24 h at 37 • C, and 5% CO 2 .…”

Section: Cell Viability Assaymentioning

confidence: 99%

Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity

Hamdy

Fayed

Mostafa

et al. 2021

IJMS

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Unfortunately, COVID-19 is still a threat to humankind and has a dramatic impact on human health, social life, the world economy, and food security. With the limited number of suggested therapies under clinical trials, the discovery of novel therapeutic agents is essential. Here, a previously identified anti-SARS-CoV-2 compound named Compound 13 (1,2,5-Oxadiazole-3-carboximidic acid, 4,4’-(methylenediimino) bis,bis[[(2-hydroxyphenyl)methylene]hydrazide) was subjected to an iterated virtual screening against SARS-CoV-2 Mpro using a combination of Ligand Designer and PathFinder. PathFinder, a computational reaction enumeration tool, was used for the rapid generation of enumerated structures via default reaction library. Ligand designer was employed for the computerized lead optimization and selection of the best structural modification that resulted in a favorable ligand–protein complex. The obtained compounds that showed the best binding to Mpro were re-screened against TMPRSS2, leading to the identification of 20 shared compounds. The compounds were further visually inspected, which resulted in the identification of five shared compounds M1–5 with dual binding affinity. In vitro evaluation and enzyme inhibition assay indicated that M3, an analogue of Compound 13 afforded by replacing the phenolic moiety with pyridinyl, possesses an improved antiviral activity and safety. M3 displayed in vitro antiviral activity with IC50 0.016 µM and Mpro inhibition activity with IC50 0.013 µM, 7-fold more potent than the parent Compound 13 and potent than the antivirals drugs that are currently under clinical trials. Moreover, M3 showed potent activity against human TMPRSS2 and furin enzymes with IC50 0.05, and 0.08 µM, respectively. Molecular docking, WaterMap analysis, molecular dynamics simulation, and R-group analysis confirmed the superiority of the binding fit to M3 with the target enzymes. WaterMap analysis calculated the thermodynamic properties of the hydration site in the binding pocket that significantly affects the biological activity. Loading M3 on zinc oxide nanoparticles (ZnO NPs) increased the antiviral activity of the compound 1.5-fold, while maintaining a higher safety profile. In conclusion, lead optimized discovery following an iterated virtual screening in association with molecular docking and biological evaluation revealed a novel compound named M3 with promising dual activity against SARS-CoV-2. The compound deserves further investigation for potential clinical-based studies.

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Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms

Cited by 17 publications

References 40 publications

Antibacterial Activity and Active Fraction of Zingiber officinale Roscoe, Zingiber montanum (J.Koenig) Link ex A., and Zingiber zerumbet (L.) Roscoe ex Sm. Against Propionibacterium acnes

Antibacterial Activity and Active Fraction of Zingiber officinale Roscoe, Zingiber montanum (J.Koenig) Link ex A., and Zingiber zerumbet (L.) Roscoe ex Sm. Against Propionibacterium acnes

Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS‐CoV‐2

Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity

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