Archiv der Pharmazie最新文献

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.

Novel biguanide hydrochloride salts were synthesized through the reaction of N-substituted-semi(thiosemi)carbazides with cyanoguanidine in an acidic medium. Antidiabetic properties of the synthesized biguanides were evaluated for their antidiabetic properties. All biguanide compounds showed promising effects, which revealed a significant decrease in the elevated glucose in comparison with metformin on oral treatment of hyperglycemic rats with the synthesized biguanide derivatives. The monosubstituted thiourea showed an improvement by about 1.48-fold of metformin. The effect of the synthesized biguanides on liver function enzyme activities, lipid profiles, and renal functions was investigated and discussed as compared with normal control rats; some urea derivatives showed improvement results that were nearly equal to those of metformin. Regarding lipid profile, the N-phenylurea moiety showed improved results higher than metformin. Regarding the effect on kidney function markers, some urea derivatives showed results that were higher than those of metformin. Also, antioxidant biomarkers and inflammatory markers were detected in diabetic rats and discussed; the results of all tested derivatives were equal to twofold of the results of metformin. Moreover, the histopathological examination of hepatic, kidney, and pancreatic tissues reveals that all of the tested compounds showed significant, promising activity.

Cancer remains a leading cause of mortality worldwide, with treatment resistance posing a major obstacle to effective therapies. Natural compounds, including quassinoids such as bruceantin and brusatol, derived from Brucea javanica (L.) Merr., have demonstrated potential as novel cancer chemopreventive agents. Bruceantin exhibits cytotoxic effects against diverse cancer cell lines, including leukemia, lymphoma, and myeloma, primarily through inhibition of protein synthesis and induction of apoptosis via caspase and mitochondrial pathways. Similarly, brusatol has shown broad-spectrum anticancer activities by modulating cellular processes such as apoptosis, cell-cycle arrest, autophagy, and attenuation of epithelial–mesenchymal transition. Mechanistically, it targets key oncogenic signaling pathways, including PI3K/AKT/mTOR and Keap1/NRF2, and enhances chemosensitivity and radiosensitivity. This review evaluates preclinical findings on the pharmacological properties, mechanisms of action, and anticancer efficacy of bruceantin and brusatol. Their structural modifications, safety profiles, and challenges such as poor bioavailability and systemic toxicity are also explored. Advances in semi-synthetic derivatives and drug delivery systems are discussed as strategies to enhance therapeutic potential. Comprehensive insights are provided into the molecular and cellular mechanisms underlying their anticancer effects, supported by in vitro and in vivo evidence. Collectively, these findings highlight the promise of bruceantin and brusatol as therapeutic agents and underscore the need for further translational research to optimize their clinical utility. These quassinoids represent a compelling avenue for the development of targeted and adjunctive cancer therapies, potentially overcoming limitations of conventional treatments.