Determination of the Inhibitory and Pharmacokinetic Properties of Helipyrone, Norhelipyrone, Italipyrone, Bisnorhelipyrone, and Plicatipyrone by in Silico Methods
2026· Brazilian Archives of Biology and Technology· Vol 69· 0 citations· 81 references
TL;DR
The molecular docking results indicated that italipyrone and plicatipyrone exhibited relatively strong binding affinities toward several target enzymes, which suggest that these compounds may be promising candidates for further experimental evaluation.
Abstract
Abstract Helichrysum stoechas (L.), commonly known as the eternal flower, has long been used in traditional medicine for the treatment of many diseases. Previous phytochemical studies have reported that H. stoechas contains a variety of secondary metabolites, including the pyrones helipyrone, norhelipyrone, bisnorhelipyrone, plicatipyrone and italipyrone, which have been isolated from the plant. In this study, the inhibitory potential of these compounds against monoamine oxidase A (MAO-A), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, cyclooxygenase-2 (COX-2), dipeptidyl peptidase-4 (DPP4), angiotensin-converting enzyme (ACE), and stable 5-lipoxygenase (stable-5-LOX) was investigated using in silico approaches, including molecular docking, molecular dynamics (MD) simulations, MM/PBSA analyses, and density functional theory (DFT) calculations. In addition, the pharmacokinetic and toxicity profiles of the compounds were evaluated using ADME/T and PASS prediction tools. The molecular docking results indicated that italipyrone and plicatipyrone exhibited relatively strong binding affinities toward several target enzymes. The MD simulations and MM/PBSA analyses revealed that the ACE-N-domain-plicatipyrone and stable-5-LOX-italipyrone complexes showed binding free energies of -42.79 and -26.32 kcal/mol, respectively. The DFT results showed favorable electronic stability characteristics for the compounds studied, while ADME/T estimates showed relatively high blood-brain barrier permeability for italipyrone and plicatipyrone, and no toxicity was predicted for the tested molecules. Overall, the findings suggest that these compounds may be promising candidates for further experimental evaluation; however, additional in vitro and in vivo studies are needed to confirm their biological activities and pharmacological potential.
Kawista (Limonia acidissima) is a plant known for its potential pharmacological properties, includingantihypertensive activity. This study aimed to evaluate the inhibitory potential of kawista secondary metabolitesagainst angiotensin-converting enzyme (ACE) using an in silico approach. A total of 31 compounds were identifiedand screened for oral bioavailability using the BOILED-Egg model, resulting in 20 compounds with favourablepharmacokinetic properties. Molecular docking analysis revealed that limodissimin A (mol 17) exhibitedthestrongest binding affinity toward ACE (−9.09 kcal/mol; Ki = 215.73 nM), with key interactions involving Lys511, His353, and His513. Molecular dynamics simulations further confirmed the stability of the ACE–ligand complex, asindicated by lower RMSD, reduced structural fluctuations, and decreased solvent exposure compared to the apoprotein. These findings suggest that limodissimin A is a promising candidate for ACE inhibition. Further experimental validation is required to confirm its potential as a natural antihypertensive agent.
E.J. Astuti, M.A. Muchlisin, D. Elvina et al.· RASAYAN Journal of Chemistry· 0 citations
Findings identify PGG and PF as two representative constituents of P. lactiflora with distinct urate-related activity profiles in enzymatic and cellular models, respectively.
Ruoling Xu, Tingting Jin, Jingwen Wang et al.· Food & Function· 0 citations
A methanol extract from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae), which is used as the crude drug Forsythiae Fructus (Forsythia Fruit; "Rengyo" in Japanese) and is listed in the Japanese Pharmacopoeia XIX, exerted enzymatic β-glucuronidase inhibitory activity. From the extract, we isolated a new diterpene rengyonoic acid (1) along with 19 known compounds including two diterpene (2 and 3), three triterpenes (4-6), seven lignans (7-13), two flavonoids (14 and 15), four phenylethanoids (16-19), and an aromatic compound (20). The structure of the new compound (1), including its absolute stereochemistry, was determined based on chemical and physicochemical evidence derived from NMR and MS spectrometry analysis as well as by comparing experimental and predicted ECD data. Among the isolates, 1 (IC50 = 117 μM), pinoresinol (7, 27.9 μM), forsythiaside A (16, 18.6 μM), and suspensaside A (19, 31.1 μM) exhibited β-glucuronidase inhibitory activity equivalent to that of a positive compound, D-saccharic 1,4-lactone (38.6 μM).
Shogo Nishikawa, Ryuya Takada, Yusuke Shimomoto et al.· Journal of Natural Medicines· 1 citation
Acetogenins are polyketides found almost exclusively in plants of the Annonaceae family and exhibit diverse biological activities, including antineoplastic, antiparasitic, cytotoxic, immunosuppressive, neurotoxic, and pesticidal effects. Five highly effective acetogenins (annopurpuricins A-E) showing anticancer properties in the picomolar range, were previously isolated from the roots of Annona purpurea (Hernández-Fuentes et al., 2019). To elucidate the mechanism underlying their potent cytotoxicity, we investigated the binding of annopurpuricins A-E to the ubiquinone-binding site of mitochondrial complex I using AutoDock Vina. Complex stability was assessed by molecular dynamics (MD) simulations. We identified the protein residues involved in binding and characterized the binding poses of the acetogenins. Annopurpuricins A-D adopted elongated conformations that spanned nearly the entire ubiquinone channel, whereas annopurpuricin E adopted a V-shaped conformation. Interactions were predominantly hydrophobic with a limited number of hydrogen bonds. These results support a model in which annopurpuricins inhibit complex I by occupying the ubiquinone channel, thus accounting for their exceptional cytotoxic potency.
Jorge Santiago Chapula-Molina, L. D. Via, H. Parra‐Delgado· Journal of Molecular Graphic...· 0 citations
Ketoconazole is a widely used antifungal drug with poor aqueous solubility, which limits its bioavailabilityandtherapeutic efficacy. Cyclodextrins like β-cyclodextrin (BCD) and its derivative 2-hydroxypropyl-β-cyclodextrin(HPBCD) are recognised for their ability to improve the solubility and stability of drugs. The objective of thisresearch was to explore the binding strength, structural integrity, and solubility improvements of ketoconazolecomplexes with BCD and HPBCD through the use of molecular docking and molecular dynamics simulations. Molecular docking was performed using AutoDock 4.2, followed by 100 ns molecular dynamics simulations inawater/octanol mixture using Amber 16. The assessments included binding energies, hydrogen bonds, hydrophobicinteractions, radius of gyration, and solvent-accessible surface area (SASA) to examine the behaviours of thecomplexes. Docking results showed stronger binding of ketoconazole–BCD (ΔG_bind = –4.56 kcal/mol) comparedto ketoconazole–HPBCD (ΔG_bind = –3.05 kcal/mol). MD simulations revealed that BCD formed a compact andstable complex with a lower radius of gyration, while HPBCD exhibited higher SASA and stronger interactions withwater molecules. Trajectory analyses confirmed that ketoconazole remained more stable in aqueous solution whenencapsulated by HPBCD. The results indicate a trade-off between structural compactness and solubilityenhancement. Although BCD forms a tighter and more rigid complex, HPBCD’s hydrophilic substituents promotegreater solvent accessibility and water affinity, leading to improved solubility of ketoconazole. These findings alignwith previous reports on cyclodextrin derivatives improving dissolution and suggest HPBCD as the more suitableexcipient for aqueous formulations. While BCD forms a tighter inclusion complex, HPBCD provides superior solubility enhancement through increased solvent interactions. These results indicate that HPBCD may be a useful additive to enhance the solubility and bioavailability of ketoconazole.
S. Sinala, A. D. Permana, S. Sartini et al.· RASAYAN Journal of Chemistry· 0 citations
This study, In-silico computational study of polyhydroxylated nortropane alkaloid from kangkong (Ipomoea aquatica) as a potential αlpha-glucosidase Inhibitor for possible blood sugar reduction via molecular docking, investigated polyhydroxylated nortropane alkaloids from Kangkong (Ipomoea aquatica) as potential α-glucosidase inhibitors for blood sugar reduction using molecular docking. Calystegine derivatives (A3, B1, B2, B3, B4, and C1) were docked against N-terminal maltase-glucoamylase (NtMGAM), C-terminal maltase-glucoamylase (CtMGAM), and N-terminal sucrase-isomaltase (NTSI) enzymes, with acarbose as the reference inhibitor. All ligands exhibited negative binding affinities, indicating stable and energetically favorable interactions. Among the derivatives, Calystegine B4 demonstrated the highest binding affinities across all targets (−6.9 kcal/mol for NtMGAM, −6.6 kcal/mol for CtMGAM, and −6.7 kcal/mol for NTSI), followed by B1 and B3, while A3, B2, and C1 exhibited moderate to low interactions. The binding energies of the calystegines were comparable to that of acarbose. Interaction analyses revealed that calystegines bind within the catalytic sites through hydrogen bonding and van der Waals interactions, suggesting a competitive inhibition mechanism. These findings identify Calystegine B4 and B1 as the most promising candidates and support the potential application of calystegine derivatives as natural α-glucosidase inhibitors for regulating post-meal blood glucose levels.
Roshane Kimberly Briz Pedregosa, Jan Criss Bongo Peralta, Rea Misamen Dela Peña et al.· International Journal of Res...· 0 citations
