Structural-based virtual screening and identification of novel potent antimicrobial compounds against YsxC of Staphylococcus aureus

Kumari, Reena; Rathi, Ravi; Pathak, Seema R.; Dalal, Vikram

doi:10.1016/j.molstruc.2022.132476

Cited by 45 publications

(12 citation statements)

References 61 publications

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“…Kumari et al. reported the five potent molecules (BDE 33512592, BDF 33512588, BDE 33512301, BDE 33512449, and BDE 33512649) against YsxC of S. aureus [9b] . Compounds (eMol26313223, eMol26314565, Naringin, Hesperidin, Neohesperidin, Didymin, and Icariin) were identified as potent molecules against penicillin‐binding protein 2a (PBP2a) of S. aureus by in silico screening [10–11] .…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Natural Product‐Like Compounds as Potential Antibacterial Agents Targeting FemC of Staphylococcus aureus: An in‐Silico Approach

Dalal

Kumari

2022

ChemistrySelect

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FemC is a methicillin resistance factor and regulates the synthesis of peptidoglycan in Staphylococcus aureus. Here, a set of natural product‐like compounds from Enamine and Selleckchem databases were screened at the active site of validated FemC model. Molecules that had interactions and good binding energies with protein were filtered by pharmacokinetic and ADMET properties. Molecular docking and molecular dynamics (MD) analysis displayed the identified molecules had stable and static interactions with FemC to form stable FemC‐inhibitor(s) complexes. Molecular Mechanics/Poisson‐Boltzmann Surface Area (MMPBSA) confirmed that identified molecules interacted with S15, M16, S17, R31, R43, Q47, K48, and R49 of FemC and resulted in the formation of lower energy complexes. The current study, hereby, reported the four (S4958 Glycocholic acid, SP‐146, Hupehenine, and Limonin) potent natural product‐like compounds that are required to be validated and may be further utilized to develop novel scaffolds for antimicrobials against S. aureus.

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Section: Discussionmentioning

confidence: 99%

Screening and Identification of Natural Product‐Like Compounds as Potential Antibacterial Agents Targeting FemC of Staphylococcus aureus: An in‐Silico Approach

Dalal

Kumari

2022

ChemistrySelect

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“…In addition to the interaction analysis, the Prime/MM-GBSA module was utilized to quantitatively assess the interaction strengths within the inhibitor/AChE complexes [ 25 – 27 ]. The computed ΔG bind values for the complexes formed between compound 8a and AChE were determined to be − 90.38 kcal/mol.…”

Section: Resultsmentioning

confidence: 99%

Anticholinesterase activities of novel isoindolin-1,3-dione-based acetohydrazide derivatives: design, synthesis, biological evaluation, molecular dynamic study

Nazarian,

Abedinifar,

Hamedifar

et al. 2024

BMC Chemistry

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In pursuit of developing novel cholinesterase (ChE) inhibitors through molecular hybridization theory, a novel series of isoindolin-1,3-dione-based acetohydrazides (compounds 8a–h) was designed, synthesized, and evaluated as possible acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. In vitro results revealed IC50 values ranging from 0.11 ± 0.05 to 0.86 ± 0.02 µM against AChE and 5.7 ± 0.2 to 30.2 ± 2.8 µM against BChE. A kinetic study was conducted on the most potent compound, 8a, to ascertain its mode of inhibition, revealing its competitive mode against AChE. Furthermore, the binding interaction modes of the most active compound within the AChE active site was elucidated. Molecular dynamics simulations of compound 8a were performed to assess the stability of the 8a-AChE complex. In silico pharmacokinetic predictions for the most potent compounds indicated their potential as promising lead structure for the development of new anti-Alzheimer’s disease (anti-AD) agents.

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“…Structure based virtual screening was conducted to prioritized chemical compound that bind best to the Pks13-TE. The combined approach of virtual screening and MDS have been used in the past to successfully screen inhibitor molecules against biological targets 45 , 62 – 64 . The Lipinski rule of five revealed total of 26,024 molecules as druglike compounds.…”

Section: Resultsmentioning

confidence: 99%

An integrated computational approach towards novel drugs discovery against polyketide synthase 13 thioesterase domain of Mycobacterium tuberculosis

Altharawi

Alossaimi

Alanazi

et al. 2023

Sci Rep

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The acquired drug resistance by Mycobacterium tuberculosis (M. tuberculosis) to antibiotics urges the need for developing novel anti-M. tuberculosis drugs that possess novel mechanism of action. Since traditional drug discovery is a labor-intensive and costly process, computer aided drug design is highly appreciated tool as it speeds up and lower the cost of drug development process. Herein, Asinex antibacterial compounds were virtually screened against thioesterase domain of Polyketide synthase 13, a unique enzyme that forms α-alkyl β-ketoesters as a direct precursor of mycolic acids which are essential components of the lipid-rich cell wall of M. tuberculosis. The study identified three drug-like compounds as the most promising leads; BBB_26582140, BBD_30878599 and BBC_29956160 with binding energy value of − 11.25 kcal/mol, − 9.87 kcal/mol and − 9.33 kcal/mol, respectively. The control molecule binding energy score is -9.25 kcal/mol. Also, the docked complexes were dynamically stable with maximum root mean square deviation (RMSD) value of 3 Å. Similarly, the MM-GB\PBSA method revealed highly stable complexes with mean energy values < − 75 kcal/mol for all three systems. The net binding energy scores are validated by WaterSwap and entropy energy analysis. Furthermore, The in silico druglike and pharmacokinetic investigation revealed that the compounds could be suitable candidates for additional experimentations. In summary, the study findings are significant, and the compounds may be used in experimental validation pipeline to develop potential drugs against drug-resistant tuberculosis.

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Structural-based virtual screening and identification of novel potent antimicrobial compounds against YsxC of Staphylococcus aureus

Cited by 45 publications

References 61 publications

Screening and Identification of Natural Product‐Like Compounds as Potential Antibacterial Agents Targeting FemC of Staphylococcus aureus: An in‐Silico Approach

Screening and Identification of Natural Product‐Like Compounds as Potential Antibacterial Agents Targeting FemC of Staphylococcus aureus: An in‐Silico Approach

Anticholinesterase activities of novel isoindolin-1,3-dione-based acetohydrazide derivatives: design, synthesis, biological evaluation, molecular dynamic study

An integrated computational approach towards novel drugs discovery against polyketide synthase 13 thioesterase domain of Mycobacterium tuberculosis

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