Archiv der Pharmazie最新文献

A series of ester derivatives of (6-methyl-4-phenyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidin-5-yl)(piperidin-1-yl) methanone (6a–6k) have been synthesized using a solvent and catalyst-free one-pot two-step synthetic method. These 11 molecules have been characterized by spectroscopic techniques such as FT-IR, NMR (¹H and ¹³C), and single-crystal x-ray structural analysis. The Hirshfeld surface and 2D fingerprint plot elucidated the intermolecular interactions and their contribution to crystal packing. Furthermore, the computational calculations, such as FMOs and MEP, revealed the global reactivity descriptors and sites for noncovalent interactions, such as hydrogen bonding, respectively, in these pharmacophores. Among these derivatives, the 6h molecule, which bears –CF₃ on the phenyl ring, has piperidine substitution on the ester group and contains a thiourea moiety, demonstrated the best larvicidal activity against Anopheles arabiensis, achieving a 94% mortality rate compared to the standard sample Temephos (98%).

Curcumin, a principal component of the Indian spice turmeric, exhibits a wide range of biological activities but suffers from poor pharmacokinetic and pharmacodynamic profiles. To overcome these limitations, monocarbonyl analogues of curcumin (MACs) have been developed through structural modifications, resulting in improved bioavailability and enhanced therapeutic potential. This review highlights recent advances in the development of MACs with a focus on their antioxidant, anti-inflammatory, antitubercular, antimicrobial, antidiabetic, antileishmanial, and anti-Alzheimer properties. Moreover, insights into their structure–activity relationships (SAR) are also discussed.

Diabetic complications are major health problems that happen to people with diabetes when their blood sugar levels stay high for a long time and damage various body organs and systems. Inhibition of aldose reductase has emerged as a promising strategy for drug development and the management of diabetes-associated complications. In the research article, a novel series of 12 compounds, “C−5-arylidene thiazolidine-2,4-dione derivatives” was constructed, synthesized, and characterized using both spectral and non-spectral techniques. The confirmed synthesized compounds were subsequently screened for in vitro aldose reductase inhibitory activity. Among them, compounds 9h and 9a exhibited superior potency against aldose reductase protein with IC₅₀ values of 0.98 and 1.05 µM, respectively, as compared with the reference drug epalrestat (IC₅₀ value of 1.20 µM). Additionally, compounds 9l and 9i showed moderate aldose reductase inhibitory activity with an IC₅₀ value of 1.36 and 2.47 µM, respectively. Furthermore, the top four best active compounds were selected for in vivo anti-hyperglycaemic activity. Results revealed that all the tested compounds significantly decreased blood glucose levels at all time intervals. Computational analysis revealed that all synthesized candidates bound firmly in the protein cavity of aldose reductase via hydrogen bonds and steric interaction with the range of docking score −10.21 to −11.81 kcal/mol. Predicted in silico toxicity data suggested that the synthesized compounds were inactive and nontoxic against peroxisome proliferator-activated receptor-γ protein. These finding results support the potential of thiazolidine-2,4-dione derivatives as promising AR inhibitors for managing diabetic complications.

A new class of kojic acid–derived tyrosinase inhibitors was rationally designed through the incorporation of a thiadiazole-urea framework. Accordingly, a series of 1-(aryl)-3-(5-{[(5-hydroxy-4-oxo-4H-pyran-2-yl)methyl]thio}-1,3,4-thiadiazol-2-yl)urea derivatives was synthesized starting from thiosemicarbazide. Through this approach, 13 new compounds were prepared with good yields via a straightforward procedure. The strategy involved substituting the hydroxymethyl group with a thiadiazol-urea pharmacophore, leading to the discovery of compounds that exhibited significantly enhanced inhibitory activity (IC₅₀ range: 0.02–0.96 µM) compared to kojic acid (IC₅₀ = 64.32 µM) against tyrosinase. Further kinetic, antioxidant, and docking studies, along with melanin content assays, were conducted to elucidate the mechanism of action for the most active compounds.

Accurate structural determination of heterocyclic scaffolds is essential for medicinal chemistry and drug discovery. In this study, products obtained from three-component reactions of aryl isothiocyanates, dialkyl acetylenedicarboxylates, and hydrazine hydrate, as well as four-component reactions incorporating aldehydes, were carefully re-examined. Previous studies had described these compounds as thiazine derivatives; however, our comprehensive synthetic and spectroscopic investigations demonstrate that they actually correspond to thiazolidinone frameworks. Key evidence was provided by gradient-selected heteronuclear multiple bond correlation (HMBC) and gated ¹³C NMR spectroscopy, which enabled the determination of regioselectivity and stereochemical features. Comparative analysis with reported X-ray crystallographic data further supported our revised assignments. These results resolve inconsistencies in earlier reports and highlight the critical importance of rigorous characterization in multicomponent heterocyclic synthesis. The findings establish a reliable framework for the identification of related heterocycles, thereby offering valuable guidance for future applications in drug-oriented synthesis and the design of bioactive molecules.

Echinacoside, a naturally occurring phenylethanoid glycoside, primarily derived from medicinal plants such as Cistanche tubulosa and Echinacea angustifolia, has long been valued in traditional medicine for its diverse pharmacological activities, including antidiabetic, anti-inflammatory, antifatigue, anti-allergic, antiaging, wound healing, and aphrodisiac effects. Recent research has steadily highlighted echinacoside's promising role as a multi-targeted oncotherapeutic agent due to its potent anticancer properties. Its antineoplastic efficacy is mediated through multiple mechanisms, including induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of key oncogenic signaling pathways such as PI3K/Akt/mTOR and MAPK/ERK. Additionally, echinacoside has significant synergistic potential with traditional chemotherapeutics, enhancing cytotoxicity while mitigating systemic toxicity and overcoming drug resistance. Despite compelling evidence for its multi-targeted anticancer mechanisms, its clinical translation is restricted by various pharmacokinetic challenges, including limited absorption and fast metabolic clearance. Although few reviews have addressed the general pharmacological activities of echinacoside, this article provides a novel and forward-looking perspective by critically bridging the gap between its multi-targeted anticancer mechanisms and its translational potential. This manuscript also comprehensively integrates the latest preclinical findings, particularly highlighting emerging nanotechnological and synergistic strategies designed to overcome its bioavailability and stability barrier, thereby uniquely outlining a strategic roadmap for future research to facilitate the clinical application of echinacoside into precision oncology.