Docking and Molecular Dynamic of Microalgae Compounds as Potential Inhibitors of Beta-Lactamase

Pestana-Nobles, Roberto; Díaz, Yani Cristina Aranguren; Sierra, Elwi Guillermo Machado; Yosa, Juvenal; Galán-Freyle, Nataly J.; Sepulveda-Montaño, Laura X.; Kuroda, Daniel G.; Pacheco‐Londoño, Leonardo C.

doi:10.3390/ijms23031630

Cited by 9 publications

(3 citation statements)

References 83 publications

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“…During the production phase, each system was run for a total of 10 ns. The final 2 ns of these simulations were utilized for the MMPBSA calculations, consistent with methodologies utilized in previous work [109,110]. This comprehensive approach helps to ensure a robust exploration of the system's phase space.…”

Section: Molecular Dynamics Configurationmentioning

confidence: 99%

A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins

Mendez-Callejas,

Piñeros-Avila,

Yosa-Reyes

et al. 2023

IJMS

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Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana) contains bioactive flavonoids that may have antioxidant and/or anti-cancer properties. This study investigated the potential anti-cancer properties of a newly identified chalcone isolated from the inflorescences of the plant Chromolaena tacotana (Klatt) R. M. King and H. Rob (Ch. tacotana). The chalcone structure was determined using HPLC/MS (QTOF), UV, and NMR spectroscopy. The compound cytotoxicity and selectivity were evaluated on prostate, cervical, and breast cancer cell lines using the MTT assay. Apoptosis and autophagy induction were assessed through flow cytometry by detecting annexin V/7-AAD, active Casp3/7, and LC3B proteins. These results were supported by Western blot analysis. Mitochondrial effects on membrane potential, as well as levels of pro- and anti-apoptotic proteins were analyzed using flow cytometry, fluorescent microscopy, and Western blot analysis specifically on a triple-negative breast cancer (TNBC) cell line. Furthermore, molecular docking (MD) and molecular dynamics (MD) simulations were performed to evaluate the interaction between the compounds and pro-survival proteins. The compound identified as 2′,3,4-trihydroxy-4′,6′-dimethoxy chalcone inhibited the cancer cell line proliferation and induced apoptosis and autophagy. MDA-MB-231, a TNBC cell line, exhibited the highest sensitivity to the compound with good selectivity. This activity was associated with the regulation of mitochondrial membrane potential, activation of the pro-apoptotic proteins, and reduction of anti-apoptotic proteins, thereby triggering the intrinsic apoptotic pathway. The chalcone consistently interacted with anti-apoptotic proteins, particularly the Bcl-2 protein, throughout the simulation period. However, there was a noticeable conformational shift observed with the negative autophagy regulator mTOR protein. Future studies should focus on the molecular mechanisms underlying the anti-cancer potential of the new chalcone and other flavonoids from Ch. tacotana, particularly against predominant cancer cell types.

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Section: Molecular Dynamics Configurationmentioning

confidence: 99%

A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins

Mendez-Callejas,

Piñeros-Avila,

Yosa-Reyes

et al. 2023

IJMS

Self Cite

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“…These techniques can anticipate the binding affinity, molecular interactions, and physiochemical characteristics of the hit compounds, saving time and money [32]. Previously, a number of in silico studies have been conducted using molecular docking and molecular dynamics simulations for the discovery of potent inhibitors of β-lactamases, particularly NDM-1, from various natural resources [34][35][36][37]. These studies have identified many phytochemicals with different chemical structures and properties that can inhibit NDM-1 [38,39], but none of them have yet been approved for use in humans.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1)

Bibi,

Asghar,

Ashraf

et al. 2023

Pharmaceuticals

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The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein–ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein–ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb–Schrödinger interaction energy, and Lennard–Jones–Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance.

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“…oil of B. vulgaris leaves and β-lactamase. A: sulfur pentafluoride; B: squalene; C: 3-aminodibenzofuran; D: 2-monolaurin; E: clavulanic acid (native) 26. Moreover, the molecular docking of eight L2-β-lactamase inhibitors shows that these compounds possess ∆G values (lowest to the highest) as follows: relebactam -6.8 kcal/ mol, meropenem -6.54 kcal/mol, nitrocefin -6.28 kcal/ mol, avibactam -6.14 kcal/mol, imipenem -5.34 kcal/mol, carbapenem -5.24 kcal/mol, ceftazidime -4.83 kcal/mol, and aztreonam -4.6 kcal/mol, respectively 27.…”

mentioning

confidence: 99%

In silico Study of Essential Oil of Bambusa vulgaris Leaves as an Anti Beta-lactamase Compound

Anggini

Amanina

Asyura

et al. 2022

Mol Cell Biomed Sci

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Background: Klebsiella pneumoniae is known as an extended spectrum beta (β)-lactamases (ESBLs)-producing bacteria, which produces enzymes that cause resistance to β-lactam antibiotics by degrading β-lactam ring. A solution is needed to prevent the degradation of the β-lactam ring. In this in silico study, combining β-lactam antibiotics with secondary metabolites has the possibility to inhibit the active site of the β-lactamase enzyme. This study aimed to explore the potential of the essential oil of yellow bamboo (Bambusa vulgaris) leaves as inhibitors of β-lactamase. Materials and methods: This research was conducted by simulating molecular docking to determine the interaction of ligands with proteins, pharmacological tests of compounds based on the Lipinski’s rule of five, and ligand toxicity tests with pkCSM. Results: The free bond energy values (∆G) were in the range of -4.3 to -8.0 kcal/mol. The ligands with the best ∆G value were sulfur pentafluoride (-8.0 kcal/mol), squalene (-7.3 kcal/mol), 3-aminodibenzofuran (-7.1 kcal/mol), and 2- monolaurin (-5.5 kcal/mol). Secondary metabolites from the essential oil of B. vulgaris leaves fulfilled Lipinski’s rule of five, so that oral use can be carried out except for squalene and tridecane. Conclusion: Secondary metabolite compounds in the essential oil that have potential as oral drugs based on the Lipinski pharmacological test and the pkCSM toxicity test are dipivaloylmethane, β-ocimene, 2-monolaurin, and undecane. Keywords: β-lactamase, Bambusa vulgaris, essential oil, Klebsiella pneumoniae

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Docking and Molecular Dynamic of Microalgae Compounds as Potential Inhibitors of Beta-Lactamase

Cited by 9 publications

References 83 publications

A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins

A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins

Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1)

In silico Study of Essential Oil of Bambusa vulgaris Leaves as an Anti Beta-lactamase Compound

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