Curcumin possesses various effective medicinal properties, such as anti-cancer, anti-Alzheimer's, anti-inflammatory, and antioxidant effects, where its free radical scavenging activities play a crucial role in its therapeutic mechanisms. Although the antioxidant properties of curcumin and its derivatives have been previously studied, a systematic investigation of the thermodynamics and kinetics of the reaction with the hydroperoxide radical (HOO˙) – a standardized free radical – in different solvents is lacking. This study examined the HOO˙ radical scavenging activities of two curcumin derivatives, specifically curcumin I (Cur-I) and curcumin III (Cur-III), in water and pentyl ethanoate (PEA) solutions using Density Functional Theory (DFT) approaches. The antioxidant properties of the neutral and anionic forms of their tautomers, including the keto–enol and diketone forms, were explored via three standard mechanisms: hydrogen abstraction (Abs), radical addition (Add), and single electron transfer (SET). Intrinsic parameters, thermochemical parameters, and kinetics of the curcumin-HOO˙ reactions were systematically characterized. As a result, the overall rate constant for the reaction of Cur-I in the water (9.36 × 10⁷ M⁻¹ s⁻¹) is approximately 3.6 times higher than that of Cur-III (2.60 × 10⁷ M⁻¹ s⁻¹). Meanwhile, the rate constants in PEA solvent are less significant, being 4.02 × 10¹ M⁻¹ s⁻¹ and 8.16 × 10² M⁻¹ s⁻¹ for Cur-I and Cur-III, respectively. Due to the dominant molar fraction of the keto–enol form compared to the diketone, the reaction rates are primarily attributed to the keto–enol form. The SET reaction of dianionic form contributes a decisive proportion to the overall rate constants of both Cur-I and Cur-III. Finally, an analysis of the chemical nature of the Abs reactions reveals that the most predominant hydrogen transfer at the phenolic –OH groups (i.e., O22H and O23H) occurs via a proton-coupled electron transfer (PCET) mechanism.

Curcuma longa is only a rich source of curcumin (1) and its major analogues demethoxycurcumin (2) and bisdemethoxycurcumin (3) among the Curcuma species. The content ratio of these three curcumins in turmeric is depended on the varieties and growing environment. Recently, curcumin (1) has been reported as potential inhibitor of hepatic and enzymatic protein tyrosine phosphatase 1B (PTP1B) and its related disorders such as hypertriglyceridemia, hyperlipidemia and liver steatosis. Thus, we further purified curcumins (1–3) from C. longa and investigated their inhibitory effects against PTP1B and α-glucosidase enzymes. As the result, curcumins (1–3) exhibited potential PTP1B inhibition with IC50 values of 37.8 ± 1.4, 45.3 ± 0.7, and 72.6 ± 1.1 μM, respectively, and α-glucosidase inhibition with similar manner (IC50 values of 78.2 ± 0.2, 82.4 ± 0.6, and 90.6 ± 1.0 μM, respectively). These results reveal a key role of methoxylation in the variation of PTP1B and α-glucosidase inhibitory activity for these curcumins. In addition, density functional theory (DFT) was used accompanying with molecular docking (MD) to analyze the ligand stability and the interaction of curcumins (1–3) with PTP1B and glucoside hydrolase proteins. Assay-based results and the MD data obtained are highly correlation suggesting that the deterioration of the enzyme activity caused by the distortion of structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in protein structure. This reported for the first time that inhibitory effects of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined in vitro and in silico as well.

Curcumin has been believed to have effective medicinal properties such as anti-cancer, anti-Alzheimer, anti-inflammatory, and antioxidant…, in which the free radical scavenging activities play a crucial role in its treating mechanisms. Although the antioxidant properties of curcumin and its derivatives have been widely studied in the literature, a systematical investigation of the thermodynamics and kinetics of the reaction towards hydroperoxide (HOO•), the standardized free radicals, has still been lacking. This work investigated the HOO• radical scavenging activities of two curcumin derivatives, namely curcumin I (Cur-I) and curcumin III (Cur-III), in water and pentyl ethanoate (PEA) solutions using Density functional theory (DFT) approaches. The antioxidant properties of the neutral and anionic forms of two tautomers, including keto-enol and diketone of curcumin, were investigated via three common mechanisms, i.e., hydrogen transfer (HT), radical adduct formation (RAF) and single electron transfer (SET). Intrinsic parameters, thermochemical parameters, and kinetics of the curcumin-HOO radical reactions were systematically characterized. As a result, the overall rate constant for the reaction in the water of Cur-I (9.36 107 M-1 s-1) is about three times higher than the one of Cur-III (2.60 107 M-1 s-1). Meanwhile, the ones in the PEA solvent are less significant, being 4.02 101 M-1 s-1 and 8.16 102 M-1 s-1, respectively. Because of the dominant molar fraction of the keto-enol form compared to that of the diketone, the reaction rates were contributed mainly by the keto-enol form. Finally, the chemical nature of the HT processes was analyzed in detail, and it was found that all the most predominant HT reactions at the phenolic -OH groups (i.e., O22H and O23H) occurred via the proton-coupled electron transfer (PCET) process.

A new spiral nematode species, Scutellonema curcumae sp. n., was identified from the rhizosphere of turmeric (Curcuma longa L.) in the Western Highlands of Vietnam. Integrative taxonomical analysis, combining detailed morphology and molecular characterization (ITS, 28S D2–D3 rDNA, and COI mtDNA), confirmed its distinctiveness. Scutellonema curcumae sp. n. is characterized by a unique combination of a spiral body, a hemispherical lip region with four annuli, a robust stylet, and a rounded tail with a prominent scutellum, forming a highly divergent lineage within the genus. Beyond its description, this study reveals a significant inverse correlation between nematode population density and the phytochemical quality of the host. High infestation levels were associated with a marked decline in total curcuminoid content. Notably, lower nematode density favored a specific shift in the curcuminoid profile, with bisdemethoxycurcumin levels increasing by up to 250%. These phytochemical alterations directly influenced the therapeutic potential of the rhizomes: lower infestation levels resulted in significantly enhanced antioxidant capacity (lower SC₅₀ values) and cytotoxic activity (lower IC₅₀ against HepG2 and A549 cell lines). This work represents the first report of a Scutellonema species associated with turmeric in Vietnam and underscores its detrimental impact on the medicinal and nutraceutical value of the crop. Our findings suggest that effective nematode management is crucial not only for yield protection but as a strategic intervention in precision agriculture to optimize the secondary metabolite profiles of medicinal plants.

Cancer represents a major global health challenge, contributing to an estimated 19 million new cases annually. While conventional chemotherapeutic approaches continue to advance, target-based therapeutic strategies are increasingly recognized as effective pathways in modern drug development. A prominent biological target in current anticancer research is the selective inhibition of Topoisomerase II alpha (TOP2A). TOP2A, a crucial DNA topoisomerase, is vital for maintaining genomic integrity by mediating the cleavage and re-ligation of double-stranded DNA during essential cellular processes, such as DNA replication and transcription. Inhibiting TOP2A effectively disrupts these processes, leading to cell death. This study employed computer-aided drug design approaches to virtually screen a library of 3000 xanthone derivatives against the TOP2A target, and the results were preliminarily validated through cytotoxicity assays on the A549 and HepG2 cancer cell lines. The computational methods utilized included molecular docking, pharmacological modeling, molecular dynamics simulations, and steered molecular dynamics simulations. The virtual screening identified two highly promising HIT compounds, CID162372098 and CID156619937, that exhibited the most favorable interactions and stability profiles in relation to the TOP2A active site. The experimental results demonstrated that both hit compounds effectively exhibited significant anti-proliferative activities against the HepG2 cell line, with IC50 values of 9.54 ± 0.26 µg mL⁻¹ (CID162372098) and 10.03 ± 0.36 12.69 ± 0.31 µg mL⁻¹ (CID156619937), respectively. Collectively, these findings demonstrate the potential of xanthone-based scaffolds as inhibitors of TOP2A and provide a rational framework for the screening and development of novel anticancer agents.

Inflammation is a key pathological process in many chronic diseases, in which the Toll-like receptor 4/myeloid differentiation factor-2 (TLR4/MD-2) complex serves as a critical upstream regulator. Curcuminoids, naturally occurring polyphenols abundant in Curcuma species cultivated in Vietnam, possess well-documented anti-inflammatory properties; however, their molecular interactions with TLR4/MD-2 remain poorly understood. In this study, an integrated in silico and in vitro strategy was employed to evaluate the anti-inflammatory potential of three major curcuminoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Molecular docking indicated that curcumin and bisdemethoxycurcumin exhibited strong binding affinities toward the TLR4/MD-2 complex, with docking scores of -9.29 and -9.73 kcal/mol, respectively. Molecular dynamics simulations further confirmed the structural stability of these complexes and revealed persistent key interactions. ADMET predictions suggested favorable drug-likeness and low toxicity profiles. Consistently, in vitro assays using LPS-stimulated RAW 264.7 macrophages demonstrated that curcumin and bisdemethoxycurcumin significantly inhibited nitric oxide production, with IC50 values of 121.06 ± 2.16 µM and 91.22 ± 1.58 µM, whereas demethoxycurcumin showed negligible activity. Overall, curcumin and bisdemethoxycurcumin emerge as promising natural compounds for the development of TLR4/MD-2-targeted anti-inflammatory agents.