In Silico Screening of Philippine Fabaceae-Derived Phenolic Acids as Potential NAGZ (Β-Hexosaminidase) Inhibitors of Neisseria Gonorrhoeae (PDB ID: 6JTJ)
2026· International journal of research and scientific innovation· Vol 13, pp. 2229-2265· 0 citations
TL;DR
Phenolic acids from Philippine Fabaceae plants were evaluated as potential inhibitors of the NagZ protein, an enzyme essential for bacterial cell wall recycling and survival, and ellagic acid, 3,4-Di-O-caffeoylquinic acid, and 4-caffeoylquinic acid showed the strongest binding and favorable pharmacokinetic properties.
Abstract
Neisseria gonorrhoeae remains a leading sexually transmitted pathogen worldwide and poses a public health challenge due to rising antimicrobial resistance. This crisis underscores the need for alternative treatment options. In this study, phenolic acids from Philippine Fabaceae plants were evaluated as potential inhibitors of the NagZ protein, an enzyme essential for bacterial cell wall recycling and survival. A total of 388 Fabaceae species obtained from Co’s Digital Flora of the Philippines were screened based on reported phenolic acid content from existing journals and literature. Among these, 92 species were identified to contain documented phenolic acids, yielding a total of 37 distinct phenolic acids. In silico analyses included molecular docking, drug-likeness, ADMET profiling, and molecular dynamics simulations. Among the candidates, ellagic acid, 3,4-Di-O-caffeoylquinic acid, and 4-caffeoylquinic acid showed the strongest binding and favorable pharmacokinetic properties. These top-performing ligands were derived from: 3,4-di-O-caffeoylquinic acid was identified from the leaf of Cassia fistula, while 4-caffeoylquinic acid was obtained from the leaves of Medicago polymorpha. Ellagic acid was remarkably prevalent, found in the flowers of Caesalpinia pulcherrima, the pods of Parkia speciosa, and more. These findings highlight their potential as lead compounds, supporting further in vitro and in vivo validation against resistant gonorrhea.
P predictive findings suggest that specific M. champaca flower constituents possess strong targeted binding potential against PTEN and CXCR4 nodes, establishing a validated computational foundation that warrants downstream in vitro and in vivo functional experimental validation.
Saketh Tenkashala Guruprasad, Karthik Punniyakoddi, V. Karthick et al.· Journal of Computational Bio...· 0 citations
Influenza A (H5N1) remains a major public health concern due to its high pathogenicity and ongoing viral evolution, underscoring the need for novel antiviral candidates.
In this study, we performed an integrated
in silico
evaluation of organosulfur compounds derived from
Allium ascalonicum
L. (shallot) cultivated in the Tolaki-Mekongga region, Sulawesi, Indonesia, targeting key viral proteins including polymerase (PB2), nucleoprotein (NP), and neuraminidase (NA).
Density functional theory (DFT) analyses were conducted to characterize the electronic properties of the compounds, while PASS prediction indicated moderate potential antiviral activity for Propanethiol and Dipropyl disulfide. Pharmacokinetic profiling suggested acceptable ADMET properties for several candidates. Molecular docking revealed favorable binding conformations across all targets, with γ-glutamyl-S-propenylcysteine exhibiting the most favorable binding energies among the evaluated organosulfur compounds (PB2: -4.9 kcal/mol; NP: -5.8 kcal/mol; NA: -5.2 kcal/mol). These values were comparable to those of oseltamivir and favipiravir for NP and NA, although weaker binding was observed against PB2. Subsequent simulations of molecular dynamics demonstrated stable protein–ligand complexes over 100 ns, further supporting the predicted binding interactions. Consistently, MM-GBSA calculations indicated favorable binding free energies, particularly for γ-glutamyl-S-propenylcysteine (PB2: -30.52 ± 0.29 kcal/mol; NP: -22.76 ± 0.12 kcal/mol; NA: -26.13 ± 0.35 kcal/mol).
Overall, these findings suggest that shallot-derived organosulfur compounds, especially γ-glutamyl-S-propenylcysteine, exhibit potential for interaction with H5N1 viral targets and may warrant further investigation as antiviral candidates. Experimental validation through
in vitro
and
in vivo
studies is required to confirm their biological activity and therapeutic potential.
Rangga Adhi Prastika, Alifaghi Pahlevi Ervianto Putra, Muhammad Alesha Fadhana et al.· Frontiers in Virology· 0 citations
Antimicrobial resistance (AMR) has emerged as a critical global health threat, necessitating the discovery of antibacterial agents with novel mechanisms of action. MurB, an essential enzyme in bacterial cell wall biosynthesis, represents an attractive target due to its absence in humans. This study aimed to evaluate the in silico antibacterial potential of α-curcumene and curdione, two bioactive constituents of turmeric essential oil, as inhibitors of the MurB enzyme. The three-dimensional structure of MurB was retrieved from the Protein Data Bank. The chemical structures of α-curcumene and curdione were obtained from the PubChem database. Molecular docking was performed using AutoDock Vina, with naphthyl tetronic acid (co-crystallized ligand) as a positive control. Binding affinities and interaction profiles were analyzed using PyMOL and Discovery Studio Visualizer. The native ligand exhibited a binding energy of -8.6 kcal/mol. Curdione demonstrated a binding energy of -6.7 kcal/mol, while α-curcumene showed -5.9 kcal/mol. Both compounds docked within the catalytic pocket, interacting with key residues Glu325, Ser229, and Arg159. Curdione exhibited superior binding affinity compared to α-curcumene. Although both compounds showed weaker binding affinity than the native ligand, their ability to occupy the MurB active site suggests they are promising lead scaffolds for antibacterial drug development. Further in vitro and in vivo studies are warranted to validate their biological activity.
Argha Rodzikin Adilaga, Annisa Mutiara Mecca, Ilham Kurniawan· Journal of Diverse Medical R...· 0 citations
Findings highlight the potential of S. burahol as a natural source of DPP-4 inhibitors, with several phenolic compounds showed strong binding affinity, particularly gallocatechol, catechin, and 6-hydroxyluteolin outperforming the native ligand.
Bintang khoirun Nadzifah, T. Sulistiyowati, P. R. Primandiri et al.· Florea Jurnal Biologi dan Pe...· 0 citations
The genus Dendrobium is a rich source of bioactive secondary metabolites, particularly bibenzyl derivatives with substantial pharmacological activities, but Dendrobium stuartii remains an underexplored species. Therefore, this study aimed to investigate the drug discovery potential of D. stuartii through an integrated in silico and experimental method. Four key compounds were prioritized through literature analysis, and the interactions with the epidermal growth factor receptor (EGFR) were evaluated using molecular docking. The chemical profile of the acetone extract was characterized using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Additionally, biological activities were assessed through antibacterial, antibiofilm, and anti-inflammatory assays. Batatasin III had the strongest predicted binding affinity toward EGFR, and the LC-HRMS analysis confirmed the presence of bibenzyl derivative 3,4ʹ-dihydroxy-5,5ʹ-dimethoxybibenzyl (gigantol). The extract provided antibacterial activity, specifically against S. aureus and P. acnes, inhibited biofilm formation during the mid-phase, and produced substantial anti-inflammatory activity, as evidenced by significant inhibition of protein denaturation. The results suggested D. stuartii as a promising underexplored source of bioactive compounds with potential applications in anticancer and anti-infective drug development.
Deni Setiawan, Samsul Hadi, Nur Mahdi et al.· Journal of Applied Pharmaceu...· 0 citations
Plant bacterial diseases threaten global food security and agricultural product quality. This study aimed to explore natural products with anti-phytopathogenic bacterial activity towards the new target guanosine monophosphate synthase (GMPS). Twelve phenolic compounds, including a new one, peniquinone L (1), were isolated using column chromatography and semipreparative HPLC from Chaetomium grande-JPT2. The molecular structures of the isolated compounds were determined by HRESIMS, 1D and 2D NMR spectrometry. High-throughput activity screening revealed that compound 11 could inhibit GMPS, yielding an EC50 value of 58.83 μg/mL. Molecular docking further revealed that the binding interaction between 11 and GMPS was primarily stabilised by two hydrogen bonds formed between the hydroxyl group in 11 and amino acid residues in GMPS. This is the first report on GMPS inhibition by phenolic compounds. Furthermore, compounds 4 and 7 displayed antibacterial activity against Xanthomonas axonopodis by two-fold serial dilution method, with MIC values of 100 μg/mL.
Wen Li, Shu-Qi Li, Mei Wang et al.· Natural Product Research· 0 citations
