Computational Screening of Styryl Lactone Compounds Isolated from Goniothalamus Species to Identify Potential Inhibitors for Dengue Virus

Abdullah, Nor Nadirah; Imran, Syahrul; Lam, Kok Wai; Ismail, Nor Hadiani

doi:10.1142/s2737416522500363

Cited by 4 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, styrylpyrone derivatives have been reported to possess cytotoxic effects on cancer cell lines. , The dihydroflavone–styrylpyrone isomers 1 – 8 were subjected to a cell viability assay using human liver cancer cell lines. No significant activity was observed against human liver cancer cells (Table ).…”

Section: Resultsmentioning

confidence: 99%

Uncovering the Power of HSCCC: Separation of Diastereomeric and Regioisomeric Styrylpyrones from the Stem Bark of Goniothalamus leiocarpus

Liu,

Li,

Zhang

et al. 2024

J. Nat. Prod.

View full text Add to dashboard Cite

The plant Goniothalamus leiocarpus of the Annonaceae family is used as an alternative medicine in tropical regions. Applying high-speed counter current chromatography (HSCCC), eight new bioactive styrylpyrone isomers, including 6R,7S,8R,2′S-goniolactone B (1), 6S,7S,8S,2′S-goniolactone B (2), 6R,7R,8R,2′S-goniolactone B (3), 6R,7S,8S,2′S-goniolactone C (4), 6R,7S,8R,2′S-goniolactone C (5), 6S,7R,8S,2′S-goniolactone C (6), and two positional isomers, 6R,7R,8R,2′S-goniolactone G (7) and 6S,7R,8R,2′S-goniolactone G (8), were isolated from a chloroform fraction (2.1 g) of G. leiocarpus, which had a prominent spot by TLC analysis. The structures of the new compounds were elucidated by MS, NMR, IR, and UV spectra, and their absolute configurations were determined by Mosher’s method, ECD, and X-ray diffraction analysis. The isolates are characteristic components found in plants of the genus Goniothalamus and consist of two structural moieties: a styrylpyrone and a dihydroflavone unit. The isolation of the eight new compounds demonstrates the effectiveness of HSCCC in separating the isomers of natural styrylpyrone. In a bioactivity assessment, compounds 1 and 6 exhibited cytotoxic effects against the human colon carcinoma cell lines LS513 and SW620 with IC50 values ranging from 1.6 to 3.9 μM. Compounds 1, 2, 7, and 8 showed significant synergistic activity against antibiotic-resistant Staphylococcus aureus strains.

show abstract

Section: Resultsmentioning

confidence: 99%

Uncovering the Power of HSCCC: Separation of Diastereomeric and Regioisomeric Styrylpyrones from the Stem Bark of Goniothalamus leiocarpus

Liu,

Li,

Zhang

et al. 2024

J. Nat. Prod.

View full text Add to dashboard Cite

show abstract

“…Although plenty of methods are available in the literature to predict the pathogenicity of mutations accurately, most of the methods do not provide a comprehensive understanding of the functional implications of these mutations. Since mutations can have complex functional consequences-for instance, they can affect the protein folding process and the binding of proteins to other macromolecules like other proteins, DNA, RNA, etc.-understanding the functional effect of mutation is essential for the drug discovery process [47][48][49][50][51][52][53][54]. In the current work, we aimed to assess the pathogenicity of a mutation using a thermodynamic approach, i.e., the change in folding free energy.…”

Section: Discussionmentioning

confidence: 99%

Most Monogenic Disorders Are Caused by Mutations Altering Protein Folding Free Energy

Pandey,

Alexov

2024

IJMS

View full text Add to dashboard Cite

Revealing the molecular effect that pathogenic missense mutations have on the corresponding protein is crucial for developing therapeutic solutions. This is especially important for monogenic diseases since, for most of them, there is no treatment available, while typically, the treatment should be provided in the early development stages. This requires fast targeted drug development at a low cost. Here, we report an updated database of monogenic disorders (MOGEDO), which includes 768 proteins and the corresponding 2559 pathogenic and 1763 benign mutations, along with the functional classification of the corresponding proteins. Using the database and various computational tools that predict folding free energy change (ΔΔG), we demonstrate that, on average, 70% of pathogenic cases result in decreased protein stability. Such a large fraction indicates that one should aim at in silico screening for small molecules stabilizing the structure of the mutant protein. We emphasize that knowledge of ΔΔG is essential because one wants to develop stabilizers that compensate for ΔΔG, but do not make protein over-stable, since over-stable protein may be dysfunctional. We demonstrate that, by using ΔΔG and predicted solvent exposure of the mutation site, one can develop a predictive method that distinguishes pathogenic from benign mutations with a success rate even better than some of the leading pathogenicity predictors. Furthermore, hydrophobic–hydrophobic mutations have stronger correlations between folding free energy change and pathogenicity compared with others. Also, mutations involving Cys, Gly, Arg, Trp, and Tyr amino acids being replaced by any other amino acid are more likely to be pathogenic. To facilitate further detection of pathogenic mutations, the wild type of amino acids in the 768 proteins mentioned above was mutated to other 19 residues (14,847,817 mutations), the ΔΔG was calculated with SAAFEC-SEQ, and 5,506,051 mutations were predicted to be pathogenic.

show abstract

“…The DFT calculations were employed by using Jaguar, version 8.7 (Schrödinger, LLC, New York, NY) (Bochevarov et al, 2013). Initial geometry was optimized using B3LYP/6-31+G* methods and basis sets (Cielecka-Piontek, et al, 2013;Abdullah et al, 2022). The compounds which showed better binding affinity in Glide-XP were taken as the input for the DFT calculations.…”

Section: Density Functional Theory (Dft) Calculationsmentioning

confidence: 99%

Computational exploration of molecular flexibility and interaction of meropenem analogs with the active site of oxacillinase-23 in Acinetobacter baumannii

et al. 2023

View full text Add to dashboard Cite

Background: Carbapenem-resistant Acinetobacter baumannii is an opportunistic pathogen responsible for nosocomial infections and is one of the biggest global threats according to the World Health Organization (WHO), particularly causing substantial morbidity and mortality.Objectives: This study aimed at using computational approaches to screen meropenem and its analogs against OXA-23-positive Acinetobacter baumannii, analyzing the correlations between kinetic and phenotypic characteristics.Methods: A total of 5,450 compounds were screened using virtual screening workflow (HTVS, Glide-SP, and Glide-XP) to identify the best compounds based on their binding energy and interactions against OXA-23 and OXA-27 as they had phenotypic data available. Molecular dynamics simulation and density functional theory (DFT) studies were performed from the outcome of molecular docking analysis.Results: During simulations, meropenem and its analogs exhibited high-level stable interactions with Ser79, Ser126, Thr217, Trp219, and Arg259 of OXA-23. Meropenem displayed a CovDock energy of about −3.5 and −1.9 kcal mol-1 against OXA-23 and OXA-27, respectively. Among the 5,450 compounds, Pubchem_10645796, Pubchem_25224737, and ChEMBL_14 recorded CovDock energy between −6.0 and −9.0 kcal mol-1. Moreover, the infra-red (IR) spectrophotometric analysis revealed C=O and C-N atoms showing bands at 1,800 and 1,125 cm-1, respectively. These observed data are in congruence with the experimental observations.Conclusion: The identified compounds showed good agreement with the spectrophotometric analysis using DFT methods. In the earlier studies, meropenem’s MIC value was 32 μg mL−1 in OXA-23-positive isolate A2265 compared to the MIC of 1 μg mL−1 in ΔblaOXA-23 A2265. Comparing the CovDock energy and hydrogen-bonding interactions, the predicted results are in good agreement with the experimental data reported earlier. Our results highlight the importance of OXA-23 molecular docking studies and their compliance with the phenotypic results. It will help further in developing newer antibiotics for treating severe infections associated with carbapenem-resistant A. baumannii.

show abstract

Computational Screening of Styryl Lactone Compounds Isolated from Goniothalamus Species to Identify Potential Inhibitors for Dengue Virus

Cited by 4 publications

References 55 publications

Uncovering the Power of HSCCC: Separation of Diastereomeric and Regioisomeric Styrylpyrones from the Stem Bark of Goniothalamus leiocarpus

Uncovering the Power of HSCCC: Separation of Diastereomeric and Regioisomeric Styrylpyrones from the Stem Bark of Goniothalamus leiocarpus

Most Monogenic Disorders Are Caused by Mutations Altering Protein Folding Free Energy

Computational exploration of molecular flexibility and interaction of meropenem analogs with the active site of oxacillinase-23 in Acinetobacter baumannii

Contact Info

Product

Resources

About