Antioxidant activity and α-glucosidase inhibitability of Distichochlamys citrea M.F. Newman rhizome fractionated extracts: in vitro and in silico screenings.

Distichochlamys citrea M.F. Newman (commonly known as "Black Ginger") is an endemic plant to Vietnam and has been extensively exploited by folk medication for treatments of infection-related diseases and diabetes. In this work, its rhizomes were subjected to fractionated extraction, phytochemical examination, evaluation of antioxidant effect by DDPH free radical neutralization, and inhibitory activity toward α-glucosidase. The compositional components were subjected to in silico screening, including density functional theory calculation, molecular docking simulation, physicochemical analysis, and pharmacokinetic regression. In the trials, EtOAc fraction is found as the bioactive part of most effectiveness, regarding both antioxidant effect (IC50 = 90.27 µg mL-1) and α-glucosidase inhibitory activity (IC50 = 115.75 µg mL-1). Chemical determination reveals there are 13 components of its composition. DFT-based calculations find no abnormal constraints in their structures. Docking-based simulation provides order of inhibitory effectiveness: 3-P53341 > 12-P53341 > 7-P53341 > 4-P53341 > 11-P53341 > 10-P53341. QSARIS-based investigations implicate their biocompatibility. ADMET-based regressions indicate that all candidates are generally safe for medicinal applications. The findings would contribute to the basis for further studies on the chemical compositions of Distichochlamys citrea and their biological activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02273-2.

Newly synthesised oxime and lactone derivatives from Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction.

Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a-3m) and 7 lactones (4, 5, 6a-6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a-3m, 4, 5, and 6a-6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC50 of 2.73 ± 0.05 µM) > 6c (IC50 of 4.62 ± 0.12 µM) > 6e (IC50 of 7.31 ± 0.11 µM), and the computation-based analysis confirmed this, i.e., 5 (mass: 416.2 amu; polarisability: 52.4 Å3; DS: -14.9 kcal mol-1) > 6c (mass: 490.1 amu; polarisability: 48.8 Å3; DS: -13.7 kcal mol-1) > 6e (mass: 549.2 amu; polarisability: 51.6 Å3; DS: -15.2 kcal mol-1). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation.

Isolation, semi-synthesis, docking-based prediction, and bioassay-based activity of Dolichandrone spathacea iridoids: new catalpol derivatives as glucosidase inhibitors.

Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea, and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12, 15) were obtained from reduction, acetylation, O-alkylation, acetonisation, or hydrolysation starting from naturally isolated compounds. They were identified by spectral methods such as IR, MS, and 1D and 2D NMR. Their glucosidase-related (3W37 and 3AJ7) inhibitability and physiological compatibility were predicted by molecular docking simulation and prescreened based on Lipinski's rule of five. Experimental α-glucosidase inhibition of 1-15 was evaluated using enzyme assays. Compounds 3, 4, 5, 6, and 9 are new iridoid derivatives, introduced to the literature for the first time, while all fifteen compounds 1-15 are studied for molecular docking for the first time. Regarding protein 3W37, the five strongest predicted inhibitors assemble in the order 2 > 10 > 1 > 9 > 14. In respect to 3AJ7, the corresponding order is 14 > 2 > 10 > 5 > 1 = 9. Lipinski's criteria suggest 10 as the candidate with the most potential for oral administration. The in vitro bioassay revealed that compound 10 is the most effective inhibitor with a respective IC50 value of 0.05 µM, in the order 10 > 2 > 14 > 13 > 1. The computational and experimental results show good consistency. The study opens an alternative approach for diabetes treatment based on inhibitability of natural and semi-synthesised catalpol iridoid derivatives towards carbohydrate-hydrolases.

Coumarin-Based Dual Chemosensor for Colorimetric and Fluorescent Detection of Cu2+ in Water Media.

A novel coumarin derivative (5) was synthesized and used as a colorimetric and fluorescent probe for selective detection of Cu2+ ions in the presence of other metal ions, with the detection limits of 5.7 and 4.0 ppb, respectively. Cu2+ ion reacts with probe 5 to form a 1:1 stoichiometry complex, resulting in a remarkable redshift of absorption maximum from 460 to 510 nm, as well as almost completely quenching fluorescence intensity of probe 5 at the wavelength of 536 nm. These changes can be distinctly observed by naked eyes. In addition, the working pH range of probe 5 is wide and suitable for physiological conditions, thus probe 5 may be used for detection of Cu2+ ions in living cells. The stable structures of probe 5 and its 1:1 complex with Cu2+ ion were optimized at the PBE0/6-31+G(d) level of theory. The presence and characteristics of bonds in compounds were studied through atoms in a molecule and natural bond orbital analysis. The formation of the complex led to a strong transfer of electron density from probe 5 as a ligand to Cu2+ ion, resulting in breaking the π-electron conjugated system, which is the cause of fluorescence quenching and color change of 5-Cu2+ complex.

Chemical constituents of Oldenlandia pinifolia and their antiproliferative activities.

This study describes the chemical constituents of Oldenlandia pinifolia (Wall. Ex G. Don) Kuntze (synonym Hedyotis pinifolia Wall. Ex G. Don) and discusses their anti-proliferative activities. Thirteen compounds were isolated from the n-hexane, ethyl acetate and n-butanol extracts of whole plants O. pinifolia by chromatography method. Their structures were elucidated using MS and NMR analysis and compared with reported data. They are three anthraquinones, a carotenoid, two triterpenes, four iridoid glycosides and three flavonoid glycosides. Among them, 2-methyl-1,4,6-trihydroxy-anthraquinone is a new one, and three compounds were found for the first time in this genus. MTT assay resulted that the n-butanol extract and four isolated compounds inhibited the proliferation of chronic myelogenous leukaemia cells. The results from Hoechst 33343 staining and caspase 3-inducing exhibited that those four tested compounds induced apoptosis and activated caspase 3 (p < 0.05). One of them, isorhamnetin-3-O-ß-rutinoside showed the most activity with IC50 value of 394.68 ± 25.12 µM.

A new rhodamine-based fluorescent chemodosimeter for mercuric ions in water media.

A new rhodamine-ethylenediamine-nitrothiourea conjugate (RT) was synthesized and its sensing property as a fluorescent chemodosimeter toward metal ions was explored in water media. Analytical results from absorption and fluorescence spectra revealed that the addition of Hg(2+) ions to the aqueous solution of the chemodosimeter RT caused a distinct fluorescence OFF-ON response with a remarkable visual color change from colorless to pink; however, no clear spectral and color changes were observed from other metal ions including: Zn(2+) , Cu(2+) , Cd(2+) , Pb(2+) , Ag(+) , Fe(2+) , Cr(3+) , Co(3+) , Ni(2+) , Ca(2+) , Mg(2+) , K(+) and Na(+) . The sensing results and the molecular structure suggested that a Hg(2+) -induced a desulfurization reaction and cyclic guanylation of the thiourea moiety followed by ring-opening of the rhodamine spirolactam in RT are responsible for a distinct fluorescence turn-on signal, indicating that RT is a remarkably sensitive and selective chemodosimeter for Hg(2+) ions in aqueous solution. Hg(2+) within a concentration range from 0.1 to 25 µM can be determined using RT as a chemodosimeter and a detection limit of 0.04 µM is achieved.

Rhodamine-derived Schiff base for the selective determination of mercuric ions in water media.

A new rhodamine-derived Schiff base (RS) was synthesized and its sensing property to metal ions was investigated by UV/vis and fluorescence spectroscopies. Addition of Hg2+ ions to the aqueous solution of RS gave a visual color change as well as significantly fluorescent enhancement, while other ions including Pb2+, Cd2+, Cr3+, Zn2+, Cu2+, Fe2+, Co3+, Ni2+, Ca2+, Mg2+, K+ and Na+ ions did not induce any distinct color/spectral changes, which constituted a Hg2+-selective fluorescent OFF-ON chemosensor. The Hg2+-induced ring-opening of spirolactam of rhodamine in RS resulted in the dual chromo- and fluorogenic observation.