Molecules最新文献

Substance Use Disorder (SUD) constitutes a major and persistent global public health burden, accounting for approximately 600,000 deaths annually, largely driven by opioid use. Despite substantial advances in addiction neuroscience, currently approved therapeutic strategies remain limited in efficacy, as they predominantly target isolated neurobiological processes and fail to concurrently address core mechanisms such as glutamatergic hyperactivity, mesolimbic hypodopaminergic, and dysfunction of cortical and executive control networks. This mechanistic fragmentation contributes to persistently high relapse rates and underscores the need for integrative and multitarget therapeutic approaches. Within this context, ibogaine has re-emerged as a clinical candidate due to its distinctive multimodal neuropharmacological profile and its reported capacity to modulate multiple pathways implicated in addictive behaviours. However, the clinical translation of ibogaine remains substantially constrained by fragmented and heterogeneous evidence, the absence of regulatory frameworks in several jurisdictions, limited phytochemical validation and standardization of available formulations, and unresolved concerns regarding cardiac safety. This scoping review critically synthesizes the available preclinical and clinical literature on ibogaine in the treatment of SUD, with particular emphasis on reported effects on withdrawal symptoms and craving, dose-response relationships, and the occurrence of cardiac adverse events. By clarifying the current state of the evidence and delineating key translational constraints, this review defines the conditions under which ibogaine, an indole alkaloid isolated from Tabernanthe iboga Baill. (Apocynaceae), may warrant continued investigation. The hypothesis of a neurobiological "reset", supported by emerging preclinical and clinical data, positions ibogaine as a compound of relevance in addiction research and highlights the need for rigorous pharmacological, toxicological, and regulatory evaluation to inform safer and more standardized clinical pathways.

Background: Medicinal plants used in traditional Mexican medicine represent a valuable source of bioactive compounds with potential anticancer activity. Beyond cytotoxic potency, selectivity toward cancer cells over normal cells is a critical toxicological parameter for identifying safer therapeutic candidates. This study aimed to evaluate the selective cytotoxic and antiproliferative effects of extracts from four Mexican medicinal plants across human cancerous and non-cancerous cell lines. Methods: Hexane, acetone, and methanolic extracts from Semialarium mexicanum, Eryngium heterophyllum, Piper auritum, and Cochlospermum vitifolium were evaluated in a panel of human cancer cell lines and non-tumoral models, including primary human uterine fibroblasts (HUFs). Cytotoxicity was assessed after 48 h of treatment using increasing extract concentrations, and selectivity indices were calculated. Cell cycle distribution and nuclear morphology analyses were performed to explore antiproliferative effects. Additionally, GC-MS-based chemical profiling was conducted on selected extracts to obtain a tentative characterization of major bioactive constituents. Results: The extracts exhibited differential cytotoxic profiles depending on plant species and solvent polarity. The hexane extract of Semialarium mexicanum showed the highest cytotoxic potency and selectivity toward cervical cancer cells, with half-maximal inhibitory concentration (IC₅₀); values of 15.9 ± 1.8 µg/mL and 17.2 ± 2.8 µg/mL in HeLa and SiHa cells, respectively, and selectivity index (SI) values > 5 when compared with primary human uterine fibroblasts (HUF). Extracts of Eryngium heterophyllum displayed moderate cytotoxic activity (IC₅₀ = 20-30 µg/mL in HeLa cells) with intermediate selectivity, whereas Cochlospermum vitifolium showed solvent-dependent effects and Piper auritum exhibited limited cytotoxicity. Cell cycle analysis revealed an increased sub-G1 population, and nuclear morphology assays demonstrated chromatin condensation and fragmentation in cancer cells, supporting an antiproliferative mechanism. GC-MS analysis of the hexane extract of Semialarium mexicanum suggested the presence of triterpenoid-related and other lipophilic compounds potentially associated with its selective anticancer activity. Conclusions: These findings provide in vitro evidence of selective anticancer activity of Mexican medicinal plant extracts and establish a basis for future mechanistic studies medicinal plant extracts and lay the groundwork for future mechanistic investigations.

Breast cancer remains the most common and leading cause of cancer deaths among women worldwide. The efficacy of conventional therapies is often hampered by off-target effects and multidrug resistance. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has gained significant attention due to its non-invasiveness, high spatiotemporal selectivity, and minimal side effects. However, its application is hindered by several obstacles, including the tumor hypoxic microenvironment, insufficient light penetration depth, and acquired heat resistance. Metal-organic frameworks (MOFs) have adjustable structures, enormous specific surfaces, and facile functionalization, providing an ideal platform to overcome these limitations. This review summarizes the latest research progress in the application of MOFs for precision phototherapy in breast cancer treatment. It emphasizes their role as a direct photosensitizer (PS), photothermal agent (PTA), or multifunctional nanocarrier for PDT, PTT, and synergistic phototherapy (including PDT/PTT, chemo/phototherapy, and immunotherapy/phototherapy). The design strategy and therapeutic effect of MOFs for phototherapy of breast cancer are critically discussed. In addition, the current bottlenecks and future perspectives are outlined to facilitate the clinical translation of MOF-based breast cancer treatment platforms.

Organometallic and metal-organic compounds are widely used in different fields of chemistry and allied disciplines, including bioinorganic and medicinal chemistry. Of particular interest is the development of novel potential anticancer agents based on palladium(II) complexes of the so-called pincer-type ligands, featuring a specific monoanionic tridentate framework. In this work, hybrid imine-thiocarbamate ligands are shown to readily undergo direct cyclopalladation in solution and under solvent-free conditions, in particular upon mechanochemical activation, yielding a series of Pd(II) pincer complexes. The latter exhibit promising cytotoxic activity against several solid and hematopoietic cancer cell lines.

With the increasing emergence of multidrug-resistant (MDR) bacteria, there is an urgent need to discover new antibiotics. In this study, genome mining coupled with anti-bacterial assay guided the targeted isolation of two new heptapeptides nobilamide Q3 (1) and R3 (2). These compounds were identified as new stereoisomers of the known scaffold A-3302-B (3). The structures of these compounds were elucidated through a combination of MS, NMR spectroscopy and Marfey's analysis. Anti-MDR bacterial assays showed that compounds 2 and 3 exhibited effective growth inhibition against the Gram-positive MDR bacterial strain Staphylococcus aureus CCARM 3090 with MIC values of 3.25-6.5 μg/mL. Notably, our study reveals stereochemistry-dependent differences in their antibacterial activities, providing new insights into the structure-activity relationship of this class of peptides. Finally, an analysis of the biosynthetic gene cluster responsible for their production was conducted. This study underscores the significance of exploring cold-seep environments as a reservoir for discovering new antibiotics and provides a structural starting point for the future optimization of antimicrobial peptides.

Iodine-based contrast agents (ICMs) are crucial substances in medical imaging because of their potent X-ray characteristics and chemical stability. However, their persistence and poor removal in conventional wastewater treatment have led to increasing environmental concern. Although ICMs exhibit low acute toxicity, their transformation during water disinfection can generate iodine-based disinfection by-products (I-DBPs), like iodo-trihalomethanes, which display notable cytotoxic, genotoxic, and ecotoxic effects and compromise drinking water quality. Advanced oxidation processes (AOPs) have become promising methods for breaking down persistent ICMs and limiting the formation of I-DBPs. Techniques including ozonation, UV/H₂O₂, UV/chlorine, photocatalysis with TiO₂, Fenton reactions, and electrochemical oxidation utilize highly reactive radicals to decompose persistent compounds like iopamidol, iohexol, iopromide, and diatrizoate. Despite high degradation efficiencies under laboratory conditions, limitations such as incomplete mineralization, secondary product formation, and elevated operational costs hinder large-scale implementation. Future research should focus on optimizing AOP conditions under realistic water matrices, evaluating by-product toxicity, and developing cost-effective hybrid systems. Advancing these technologies is critical to reducing the environmental burden of ICMs and safeguarding aquatic ecosystems and public health.

Bisacurone is a sesquiterpenoid constituent of Curcuma longa that has received considerably less attention than curcuminoids despite emerging evidence of its biological activity. In this study, the anti-inflammatory potential of bisacurone isolated from the Ryudai gold variety of Curcuma longa was evaluated using an integrated in vivo and in silico approach. Acute inflammation was assessed in rats using a carrageenan-induced paw edema model, supported by histopathological examination of paw tissues. Bisacurone significantly reduced paw edema during the peak inflammatory phase and markedly attenuated dermal thickening and inflammatory cell infiltration, indicating effective suppression of acute inflammatory responses. The effects of bisacurone were comparable to that of indomethacin. To elucidate the underlying molecular basis, density functional theory calculations, molecular docking, molecular dynamics simulations, and pharmacokinetic and toxicity predictions were performed. In silico analyses revealed favorable electronic properties, drug-likeness, and stable interactions of bisacurone with key inflammatory regulators, particularly IKKβ and COX-1, along with moderate interactions with MAPKs and iNOS. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes. Collectively, these findings demonstrate that bisacurone exerts anti-inflammatory effects through multi-target modulation of inflammatory signaling pathways and highlight its potential as a bioactive functional food component and a lead compound for anti-inflammatory drug development.

Cancer remains a significant global health crisis, being one of the foremost causes of mortality [...].

This study explores the multifaceted anticancer mechanisms of flavanone analogues and spiropyrazoline condensed with flavanone ring against colorectal cancer (CRC) cell lines. Five-membered heteroaromatic scaffolds, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. Building upon previous findings, we investigated three lead derivatives (1, 3, and 5) with potent antiproliferative activity (IC₅₀ < 35 μM). The compounds induced pronounced oxidative stress, evidenced by increased lipid peroxidation and reduced membrane fluidity, primarily within the hydrophobic layers of cell membranes. Preincubation with the antioxidant N-acetylcysteine (NAC) significantly attenuated these effects, confirming the pivotal role of reactive oxygen species (ROS) in their cytotoxicity. Mechanistic studies revealed that the derivatives triggered intrinsic apoptosis, characterized by the cleavage of PARP and the activation of caspase-9 and caspase-3. Furthermore, the compounds modulated key signaling pathways involved in cell survival and proliferation. Specifically, they inhibited the pro-oncogenic ERK1/2 MAPK pathway while inducing cell line-dependent alterations in p38 and JNK activity. Concurrently, all derivatives reduced the level of the transcription factor Nrf2, a master regulator of antioxidant defense and a mediator of chemoresistance in CRC. Collectively, these findings indicate that flavanone/chromanone derivatives exert their anticancer activity through a synergistic mechanism involving ROS generation, disruption of redox homeostasis, inhibition of Nrf2 signaling, and modulation of MAPK-dependent apoptotic pathways. These results highlight the therapeutic potential of flavanone-based compounds and their spiropyrazoline analogues as multifunctional anticancer agents targeting oxidative stress and survival signaling in colorectal cancer.

Polyphenolic compounds have long been recognized as one of the most structurally diverse and biologically relevant classes of secondary metabolites in plant-derived foods and natural products [...].