In vitro and in silico studies of alpha glucosidase inhibition and antifungal activity of coffea canephora husk.

The coffea canephora husk, a protected agricultural crop, is abundant in Vietnam. Examining the effects of C. canephora husk compounds on α-glucosidase and antifungal drug activity was the primary objective of this research. A cholestane-type steroid, coffeacanol A (1), was extracted from the ethyl acetate extract. Three cholestane-type derivatives (2-4) and three additional known compounds (5-7) were separated, and we used a variety of chromatographic techniques to identify a total of six substances. We used NMR to determine the chemical structures of these substances. Extensive HR-MS-ESI analysis and NMR experimental data were used to confirm the structure of the novel metabolite (1). The cholestane-type steroid was initially discovered in the Coffea canephora husk, marking the first instance in the coffee plant family to reveal chemical structures (1-7). The inhibition of α-glucosidase was found to be significantly higher in all compounds tested, with the exception of compounds (2) and (5). In vitro, the positive control showed the lowest inhibition, and the range of IC50 values was calculated to be 27.4 to 96.5 µM, which is lower than the IC50 value of 214.50 µM for the acarbose control. With an IC50 value of 27.4 µM, compound (7) showed the greatest capacity to inhibit α-glucosidase among the test compounds. The 3TOP and 2VF5 enzyme crystal structures were used for in silico docking investigations and validations of compounds (1-7). In silico calculations to explain how compound (7) shows high activity in vitro via the enzyme inhibition mechanism by residual amino acids, like Gly 1102 (B chain) and Glu 1095 (B chain), and their relative interaction with compounds (7) and acarbose. Compound (7) exhibited the best antifungal activity against Candida albicans fungus among three fungi, namely Candida albicans, Trichophyton mentagrophytes, and Trichophyton rubrum, with a MIC value of 25 µM. Compound (7) and fluconazole combined to form similar interactions in the contact ligand model, including the functional group, capping group, and linker part, which interacted fully with the 2VF5 enzyme, leading to effective in vitro inhibition.

In vitro and in silico docking and molecular dynamic of antimicrobial activities, alpha-glucosidase, and anti-inflammatory activity of compounds from the aerial parts of Mussaenda saigonensis.

Twelve compounds were isolated from Mussaenda saigonensis aerial parts through phytochemical analysis and the genus Mussaenda is the first place where the compounds 4-6 and 11-12 have been found. Based on the ability to inhibit NO production in RAW264.7 cells, compound 2 has demonstrated the strongest anti-inflammatory activity in vitro with an IC50 of 7.6 µM, as opposed to L-NMMA's IC50 of 41.3 µM. Compound 12 was found to be the most effective inhibitor of alpha-glucosidase enzyme in vitro, with an IC50 value of 42.4 µM (compared to 168 µM for acarbose). Compounds 1-12 were evaluated in vitro for antimicrobial activity using the paper dish method. Compound 11 demonstrated strong antifungal activity against M. gypseum with a MIC value of 50 µM. In silico docking for antimicrobial activity, pose 90 or compound 11 docked well to the 2VF5 enzyme, PDB, which explains why compound 11 had the highest activity in vitro. Entry 2/pose 280 demonstrated excellent anti-inflammatory activity in silico. The stability of the complex between pose 280 and the 4WCU enzyme for anti-inflammatory activity has been assessed using molecular dynamics over a simulation course ranging from 0 to 100 ns. It has been found to be stable from 60 and 100 ns. The Tyr 159 (95%, H-bond via water bridge), Asp 318 (200%, multiple contacts), Met 273 (75%, hydrophobic interaction via water bridge), and Gln 369 (75%, H-bond via water bridge) interacted well within the time range of 0 to 100 ns. It has more hydrophilic or polar pharmacokinetics.

Correction: Antimicrobial and alpha-glucosidase inhibitory flavonoid glycosides from the plant Mussaenda recurvata: in vitro and in silico approaches.

[This corrects the article DOI: 10.1039/D4RA00666F.].

Antimicrobial and alpha-glucosidase inhibitory flavonoid glycosides from the plant Mussaenda recurvata: in vitro and in silico approaches.

Seven flavonoid glycosides were isolated from the aerial portions of Mussaenda recurvata during a phytochemical analysis. This comprised one novel component, ecurvoside, and six well-studied compounds, namely astragalin, isoquercitrin, nicotiflorin, rutin, hesperidin, and neohesperidin. The chemical structures of compounds were identified using spectroscopic techniques and a comparison with previously published studies. Alpha-glucosidase inhibition testing was carried out on all isolated compounds. The compounds evaluated have IC50 values between 35.6 and 239.1 g mL-1, indicating a moderate degree of inhibition. In vitro antimicrobial activities of compounds 1-7 have screened against the bacteria Pseudomonas aeruginosa (P. aeruginosa), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus faecalis (Strep. faecalis), and fungi: Candida albicans (C. albicans), Trichophyton mentagrophytes (T. mentagrophytes), and Microsporum gypseum (M. gypseum), where compound 6 showed excellent activity against fungi T. mentagrophytes with an MIC value of 12.5 µM. In accordance with the molecular docking study, ecurvoside (1) or pose 472 interacted well with the 3TOP enzyme: PDB and the molecular dynamic simulations proved that the complex of ecurvoside and 3TOP has a stable simulation time of 50-100 ns and the significant residual amino acids in 3TOP are relative to interactions more than one time such as Asp 960, Glu 961, Lys 1088, Glu 1095, Arg 1097, Gly 1102, Thr 1103, Gln 1109, Glu 1178: A chain and Glu 1095, Thr 1101, and Asp 1107: B chain. The docking studies of compounds 1-7 to the enzyme 2VF5 explain the general mechanism to inhibit bacteria and proved that compound 6 (pose 370) inhibited stronger than compound 7 (pose 362) and compound 5 (pose 280), and compounds 1 to 4 do not interact well with 2VF5.

In vitro anti-inflammatory, in silico molecular docking and molecular dynamics simulation of oleanane-type triterpenes from aerial parts of Mussaenda recurvata.

Bioactive-guided investigation of the aerial parts of Mussaenda recurvata Naiki, Tagane, and Yahara (Rubiaceae) led to the isolation of four triterpenes, including two new triterpenes recurvatanes A and B (1 and 2), along with two known compounds 3ß,6ß,23-trihydroxyolean-12-en-28-oic acid (3) and 3ß,6ß,19α,23-tetrahydroxyolean-12-en-28-oic acid (4). The chemical structures of the compounds were identified from spectroscopic data and by comparison with the literature. A comprehensive review of NMR data of the oleanane-type triterpenes bearing 3-hydroxy and 4-hydroxymethylene groups indicated the characteristic spectroscopic features in this series. Compounds 1-4 were evaluated for the inhibitory NO production in LPS-stimulated RAW264.7 cells. Compounds 2 and 3 showed a moderate reduction of nitrite accumulation with IC50 values of 55.63 ± 2.52 and 60.08 ± 3.17 µM, respectively. Molecular docking model dedicated to compound 3 or pose 420, which is the best candidate among docking poses of compounds 1-4 interacted well with the crystal structure of enzyme 4WCU: PDB. The best ligand molecule, pose 420 in terms of binding energy obtained from docking studies on molecular dynamics (MD) simulations for 100 ns exhibited non-bonding interactions with the protein and remained stable inside the active site.

Bio-guided isolation of alpha-glucosidase inhibitory compounds from Vietnamese Garcinia schomburgkiana fruits: in vitro and in silico studies.

Garcinia schomburgkiana is an edible tree widely distributed in the southern region of Vietnam. Little is known about the alpha-glucosidase inhibition of the Vietnamese Garcinia schomburgkiana. The aim of the current study was to explore the anti-diabetic potential of G. schomburgkiana fruits. All the fractions of G. schomburgkiana were evaluated for alpha-glucosidase inhibition, followed by bioassay-guided isolation. A new compound, epi-guttiferone Q (1), together with ten known compounds, guttiferones I-K (2-3), hypersampsone I (4), sampsonione D (5), sampsonione H (6), ß-mangostin (7), α-mangostin (8), 9-hydroxycalabaxanthone (9), and fuscaxanthone (10), were isolated and structurally elucidated. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. To the best of our knowledge, the metabolites (except 3) have not been isolated from this plant previously. All isolated compounds were evaluated for their alpha-glucosidase inhibition. Compounds 1-6 showed potent activity with IC50 values ranging from 16.2 to 130.6 µM. Compound 2 was further selected for a kinetic study. The result indicated that it was a competitive type. Additionally, in silico docking was employed to predict the binding mechanism of 1-2 and 4-6 in the active site of alpha-glucosidase, suggesting their potential as promising anti-diabetic compounds. Molecular dynamic simulation was also applied to 1 to better understand its inhibitory mechanism.

Supercritical CO2 assisted extraction of essential oil and naringin from Citrus grandis peel: in vitro antimicrobial activity and docking study.

The extraction of bioactive compounds, including essential oils and flavonoids, using organic solvents is a significant environmental concern. In this work, waste C. grandis peel was the ingredient used to extract essential oil and naringin by conducting a supercritical CO2 technique with a two stage process. In the first stage, the extraction with only supercritical CO2 solvent showed a significant enhancement of the d-limonene component, up to 95.66% compared with the hydro-distillation extraction (87.60%). The extraction of naringin using supercritical CO2 and ethanol as a co-solvent was done in the second stage of the process, followed by evaluating in vitro antimicrobial activity of both the essential oil and naringin. The essential oil indicated significant activity against M. catarrhalis (0.25 mg ml-1), S. pyogenes (1.0 mg ml-1), S. pneumoniae (1.0 mg ml-1). Whilst naringin gave good inhibition towards all tested microbial strains with MIC values in the range of 6.25-25.0 µM. In particular, naringin exhibited high antifungal activity against T. rubrum, T. mentagrophytes, and M. gypseum. The molecular docking study also confirmed that d-limonene inhibited bacterium M. catarrhalis well and that naringin possessed potential ligand interactions that proved the inhibition effective against fungi. Molecular dynamics simulations of naringin demonstrated the best docking model using Gromacs during simulation up to 100 ns to explore the stability of the complex naringin and crystal structure of enzyme 2VF5: PDB.