Chemistry & Biodiversity最新文献

Mutations in isocitrate dehydrogenase genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML), occurring in up to 30% of AML cases. Mutations in IDH lead to abnormal epigenetic regulation in AML cells and block differentiation. Inhibitors of mutated IDH1 and IDH2, vorasidenib, ivosidenib, olutasidenib, and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML. In this review, we mainly focus on IDH inhibitors in leukemia therapy, including the discovery, structure optimization, activity of IDH inhibitors, and applications, which provided the reference for the discovery of new anticancer agents.

Worldwide, cancer is a leading cause of morbidity and mortality. While multiple EGFR inhibitors have emerged, their therapeutic efficacy is constrained by the development of drug resistance and long-term toxicity. Indoles have been identified as one of the promising scaffold classes to compete against EGFR in terms of selectivity and potency. They are favorable for anticancer drug discovery because they are structurally plastic, possess favorable pharmacokinetics, and bind to the ATP-binding pocket of EGFR. Indole derivatives inhibit the auto-phosphorylation of EGFR, thereby exhibiting their activity against cancers by blocking cancer cell proliferation, survival, and metastasis. The translation potential of this scaffold is also supported by the clinical success of indole-based EGFR inhibitors, including the third-generation drug osimertinib. Recent advances in molecular docking, structure-activity relationship studies, and hybrid drug design highlight the potential of indole-based scaffolds to address resistance mutations while minimizing side effects. This paper summarizes the relevant literature of indole EGFR inhibitors published between 2021 and 2025, which may include mechanistic insights, biological screening, and therapeutic potential. The indole scaffold can be a useful starting point to push forward the next generation of targeted cancer therapies.

Artabotrys species have been traditionally used for managing diabetes; however, their bioactive components remain insufficiently explored. This study evaluated the antihyperglycemic potential of Artabotrys hexapetalus and Artabotrys siamensis leaf extracts by identifying their major active components and assessing their inhibitory effects on key carbohydrate-metabolizing enzymes through gas chromatography-mass spectrometry profiling, docking, and in vitro assays. Metabolite profiling revealed brassicasterol (19.33%), β-caryophyllene (12.3%), 1-hexacosanol (10.82%), and chondrillasterol (8.62%) as major compounds in A. hexapetalus, whereas A. siamensis showed 22-dihydrospinasterol acetate (8.13%), 1-hexacosanol (6.55%), and brassicasterol (6.47%). Molecular docking studies revealed strong binding affinities of phytosterols (brassicasterol, chondrillasterol, and 22-dihydrospinasterol acetate) to α-amylase and α-glucosidase with binding energies ranging from -7.4 to -9.2 kcal/mol, outperforming the reference drug acarbose. In vitro inhibition assays confirmed that A. hexapetalus demonstrated superior inhibition of both enzymes with half-maximal inhibitory concentration values (IC₅₀) of 0.139 and 0.255 mg/mL for α-amylase and α-glucosidase, respectively, compared to A. siamensis (0.249 and 0.709 mg/mL) and acarbose (0.084 and 0.551 mg/mL), respectively. These findings suggest promising antihyperglycemic potential of A. hexapetalus and A. siamensis, attributed to their bioactive phytosterols in their hexane extracts.

Chronic diabetes, often linked to oxidative stress and microbial infections, requires safer, multifunctional therapies. Parthenium hysterophorus L., a member of the Asteraceae family, has long been used in traditional medicine for its therapeutic properties. This study explores its potential in managing diabetes and related complications. Chemical analysis revealed hydroxyl-rich compounds, such as phenols and phenolic acids, with a prominent Fourier transform infrared (FTIR) band at 3378.8 cm^-1. The ethyl acetate fraction (EAF) and AQF fractions exhibited significant antioxidant activity (IC₅₀: 14.71 ± 0.64 and 33.4 ± 0.89 µg/mL) and significant antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa (minimum inhibitory concentration: 312.5 µg/mL). Notably, the EAF fraction showed anti-biofilm activity (IC₅₀: 3110 ± 0.10 µg/mL) and potent α-glucosidase inhibition (IC₅₀: 0.112 ± 0.006 µg/mL). Molecular docking revealed that ferulic acid exhibited the highest binding affinity for the 3TOP transcriptional regulator's active site (-6.309 kcal/mol), while vanillic acid interacted robustly with the 2UV0 and 4F5S enzymes (docking scores: -6.299 and -6.161 kcal/mol). Cluster analysis confirmed stable binding clusters, particularly for ferulic acid. MD simulations revealed minimal RMSD fluctuations and favorable solvent accessible surface area (SASA) values, indicating stable complex formation and significant interaction stability. Ferulic acid showed the most favorable binding with the 3TOP enzyme, reinforced by hydrophobic and hydrogen bonding interactions. In case of pure compounds tested, ferulic acid demonstrated significant biofilm (IC₅₀: 3.25 ± 0.54 µg/mL) as well as α-glucosidase inhibition (IC₅₀: 0.067 ± 0.0013 µg/mL). Cytotoxicity assays on HEK293 (human embryonic kidney cells) showed no significant viability reduction at 2.5% concentration, but a 74% reduction at 10%, indicating dose-dependent cytotoxicity. These findings suggest P. hysterophorus L. as a promising natural source for multifunctional therapies targeting oxidative stress, infections, and hyperglycemia, with ferulic acid as a potent bioactive compound. Further studies on pharmacokinetics and pharmacodynamics are warranted to evaluate its therapeutic potential.

In the current study, we have designed three hitherto unreported, aldimine-based zinc complexes, used as precursors to prepare the corresponding zinc oxide nanomaterials. The complexes are further assessed for binding propensity with BSA and human serum albumin (HSA), the homologous proteins. The interactions with plasma proteins indicate the drug-like behaviour of the complexes and play a significant role in drug design and pharmacology research. Both proteins possess typical physicochemical properties and functions, acting as drug carriers in plasma. UV absorption titration and fluorescence quenching studies have been used to investigate the interaction of zinc complexes with both proteins. From the results, it has been observed that the ZnHL3 complex shows higher binding constants than the other complexes. Drug loading is a promising approach for developing amorphous pharmaceuticals that are highly stable and have enhanced bioavailability, solubility, and dissolution rates. Hence, we have assessed the relative curcumin loading abilities of complex/nanomaterial-coated BSA.

Five Siraitia grosvenorii polysaccharides (SGPs), namely, SGP-H, SGP-A, SGP-B, SGP-E, and SGP-U, were extracted from hot air-dried fruits using hot water extraction (HWE), acid-assisted extraction (ACAE), alkaline-assisted extraction (ALAE), enzyme-assisted extraction (EAE), and ultrasonic-assisted extraction (UAE), respectively. The extraction yields of ACAE and ALAE were 1.65- and 1.59-fold higher than that of traditional HWE, respectively. Monosaccharide composition analysis showed that SGP-H, SGP-A, SGP-E, and SGP-U were acidic heteropolysaccharides composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose with a notable discrepancy in the molar ratio, whereas SGP-B exhibited the lowest uronic acid content and a unique monosaccharide profile dominated by glucose (76.62%). Comprehensive characterization confirmed significant differences in molecular weight, glycosidic linkage, and surface morphology among the five SGPs. Antioxidant assays indicated that SGP-B exhibited the stronger ABTS and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity than the other SGPs, with EC₅₀ values of 416 ± 5.4 and 338 ± 14.8 µg/mL, respectively. Meanwhile, immunomodulatory studies on RAW264.7 macrophages revealed that SGP-B significantly enhanced phagocytosis by 29% and stimulated the secretion of immune factors. Therefore, SGP-B, obtained via ALAE, shows great application potential in the development of antioxidants and immunomodulators, and further research deserves attention.