Jul 2026· Journal of Applied Pharmaceutical Sciences· Vol 16, pp. 566 - 580· 0 citations· 89 references
TL;DR
The results suggested D. stuartii as a promising underexplored source of bioactive compounds with potential applications in anticancer and anti-infective drug development.
Abstract
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.
Numerous reports of drug resistance in Leishmania major, the causative agent of cutaneous leishmaniasis (CL), underscore the need to discover novel therapeutics. Fungal secondary metabolites (SMs) are valuable resources for drug development and can serve as antimicrobial agents, enzyme inhibitors, and lead compounds for novel medicines. A three-dimensional model of the L. major sterol 14α-demethylase (LmCYP51) enzyme was built using L. infantum CYP51 as a template. A library of 1,167 compounds was virtually screened against LmCYP51 using high-throughput docking. Eleven promising candidates were identified and further analyzed through 100-ns molecular dynamics simulations. Six high-affinity candidates were selected for experimental validation. In vitro assays, including MTT, Giemsa staining, and flow cytometry, were performed to evaluate antiparasitic efficacy. Dihydrocitrinone emerged as the most promising compound with the most negative predicted binding free energy (ΔG = -35.41 kcal/mol) and the most potent in vitro activity, with IC50 values of 9.87 and 26.29 µM against promastigotes and intracellular amastigotes, respectively. The compound exhibited moderate selectivity (selectivity index = 2.8). Flow cytometric analysis revealed that dihydrocitrinone, at its IC50 concentration, promotes phosphatidylserine externalization and induces apoptosis-like programmed cell death in 86% of cells. By integrating computational prioritization with experimental validation, this study identified dihydrocitrinone, a fungal polyketide, as an early antileishmanial hit against L. major that induces apoptotic-like programmed cell death. Dihydrocitrinone's promising antileishmanial potency provides a suitable scaffold for medicinal chemistry optimization and the development of novel therapeutics for leishmaniasis. This research provides the first experimental validation of dihydrocitrinone against L. major and highlights the underexplored potential of fungal SMs in antileishmanial drug discovery.
Parastoo Hassani-Abharian, Mustafa Ghanadian, A. Fassihi et al.· Scientific Reports· 0 citations
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
Fungal infections pose a growing global health threat, worsened by rising antifungal resistance and a limited therapeutic arsenal. Squalene epoxidase (SQLE), an enzyme essential for ergosterol biosynthesis, is a validated antifungal target exploited by drugs such as allylamines and benzylamines. This study aimed to perform an in silico prospection of natural antifungal compounds through molecular docking to identify potential SQLE inhibitors of Candida albicans among thirteen selected phytocompounds, compared against five reference antifungals (terbinafine, naphthifine, butenafine, tolciclate, and liranaftate). The SQLE structure (UniProt Q92206) was obtained via AlphaFold prediction, and its binding pockets were identified using PrankWeb, followed by molecular docking and intermolecular interaction analysis with BIOVIA Discovery Studio; toxicity was predicted using ProTox 3.0 and STopTox. Isorhamnetin, baicalin, apigenin-7-O-glucoside, and silibinin showed the most promising binding affinities, converging on key active-site residues (ASP332, VAL45, PRO339) shared with reference antifungals, while displaying a distinct interaction profile dominated by hydrogen bonding rather than hydrophobic contacts. These phytocompounds also showed favorable predicted toxicity profiles, with low acute toxicity and no organ-specific toxicity alerts. The findings support the potential of these flavonoids as selective, low-toxicity SQLE inhibitor candidates and reinforce the value of in silico screening in guiding future in vitro and in vivo validation of novel antifungal therapies derived from plant biodiversity.
L. Oliveira, Agueda Maria de França Tavares, Aderson Vasconcelos Santos et al.· Revista de Estudos Interdisc...· 0 citations
Tuberculosis (TB) is one of the most serious global health issues, with
the increasing number of multidrug-resistant TB cases emphasizing the need for new therapeutic
approaches. Phytochemicals, with their diverse structures and favorable safety profiles, are a
largely unexplored area for anti-TB drug development.
An ethnobotanical study and literature analysis identified 310 medicinal plants
traditionally used to treat respiratory infections, which produced 4,087 phytochemicals. Their
structures were obtained from PubChem or drawn using ChemDraw, and pharmacokinetic
properties were analyzed using QikProp. Enoyl-acyl carrier protein reductase (InhA, PDB ID:
4TRO), an important enzyme involved in mycolic acid biosynthesis, was selected as the target
protein. Molecular docking was performed using Glide, followed by MMGBSA calculations,
and the best hits were validated by 300 ns molecular dynamics simulations using the
GROMACS pipeline.
Binding affinities showed that four phytochemicals, namely Patuletin, skimmin, flavonol-
3-O-D-glycoside, and salicin, had significantly higher binding affinity scores (-10.06
to -8.82 kcal/mol) than first-line anti-TB drugs isoniazid (-6.35 kcal/mol) and pyrazinamide
(-4.22 kcal/mol). Patuletin and skimmin had MM-GBSA binding affinity scores of -74.89 and
-71.76 kcal/mol, respectively. MD simulations of the top 3 compounds and control showed that
the protein-ligand complexes were stable, as indicated by the RMSD, RMSF, Radius of gyration,
SASA, and HBONDS.
Patuletin and Skimmin demonstrated strong binding affinity and structural stability
against the InhA enzyme (PDB: 4TRO), indicating their potential as promising lead compounds
for anti-tuberculosis effects. Derived from ethnomedicinal plants, these phytochemicals not only
target key mycobacterial pathways but may also offer hepatoprotective and immunomodulatory
benefits. The findings support the exploration of plant-derived compounds as safer and effective
alternatives or adjuncts to conventional anti-TB therapies.
The combination of virtual screening, ADME studies, and MD simulations
enabled the identification of phytochemicals with promising interactions toward InhA, an
established anti-TB target. The findings are based solely on computational analysis and should
be interpreted as preliminary evidence of target engagement rather than confirmed inhibitory
activity or therapeutic efficacy. These natural products may serve as potential lead compounds
for further anti-tubercular drug discovery, warranting subsequent biochemical, cellular,
and in vivo validation to establish their inhibitory potential, safety, and pharmacological effectiveness.
Unknown authors· Current Computer - Aided Dru...· 0 citations
In-silico integration approach revealed the therapeutic potential of grass-derived endophytic fungal metabolites and prioritized potent candidates for future agricultural and pharmacological validation, highlighting endophytes as valuable sources of natural compounds for the development of antimicrobial and antioxidant agents.
Aishwarya K. Kamunkar, R. Nischitha· Archives of Microbiology· 0 citations
Six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum are investigated using an integrated in silico approach to evaluate their therapeutic potential, highlighting the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ.
A. Amin, H. M. Amin, A. R. Hamad et al.· Technology and Health Care· 0 citations
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