Current Topics in Medicinal Chemistry - Online First

Skin wounds represent a worldwide problem. Biopolymers have been attracting interest in healthcare products for wound dressing. Among these, bacterial nanocellulose membranes (BNC) are attractive for their unique structure, but they lack antimicrobial activity. Thus, the incorporation of the monoterpenes Carvacrol (Car) and Thymol (Thy) - which present antimicrobial and healing properties - toward the improvement of skin wound healing, consists of an appealing approach. This research aimed to produce and characterize nanocellulose membranes containing carvacrol and/or thymol, and investigate their release behavior, cytotoxicity, and antimicrobial properties.

BNC/Car, BNC/Thy, and BNC/Car-Thy membranes were produced at doses of 0.1 and 1.0 mg/cm².

The natural components incorporation into the nanocellulose did not interfere with the ultra-structure or its physical characteristics. Pilot studies showed that membranes with 1.0 mg/cm² of monoterpenes were toxic to fibroblasts. Therefore, all further studies used the lower dose of 0.1 mg/cm². Release experiments showed a burst release between 2-4 h with sustained release till 24 h, reaching around 80% of the initial amount of the incorporated monoterpenes. Studies with fibroblast and keratinocytes indicated no cytotoxicity and that cells could proliferate over the BNC/Car-Thy membranes. Microbiological studies suggested some antimicrobial potential of the BNC doped with Car and Thy.

BNC membranes incorporated with Car and Thy were successfully produced and the monoterpenes incorporation into the BNC did not interfere with either ultra-structure or with its physico-chemical characteristics. Natural products incorporation induced cell proliferation and presented antimicrobial properties, besides increasing the solubility and stability of these natural compounds.

This innovative biomaterial has the potential for healthcare products.

The ethyl acetate extract of Wenxia Formula (WFEA) is the most effective antitumor component of the Wenxia formula. Its key active components, emodin and quercetin, exhibit unique advantages in targeting TGF-β1 and regulating the function of Tregs. This study explored the mechanism of WFEA in enhancing the immune environment in lung cancer by influencing immune cell balance and the level of cytokines.

Lewis lung cancer xenograft mouse models were established. WFEA was administered at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, while a cisplatin (DDP) group served as the positive control. Tumor weight, spleen index, and serum cytokine levels (IL-10, TGF-β1) were measured. Flow cytometry, qPCR, and immunohistochemistry were employed to analyze the proportion of CD4⁺CD25⁺Foxp3⁺ Treg cells and Foxp3 expression in tumor and spleen tissues. The regulatory mechanism of WFEA on the TGF-β/Smads signaling pathway was investigated via combined intervention with the TGF-β1 inhibitor halofuginone (HF), cell differentiation assays, and molecular docking analyses.

WFEA inhibited tumor growth in a dose-dependent manner, with the 400 mg/kg group exhibiting a 60% tumor inhibition rate comparable to that of DDP. The agent significantly increased the spleen index by 106.42% and reduced serum levels of IL-10 and TGF-β1. Mechanistically, WFEA downregulated Foxp3 mRNA and protein expression in both tumor and spleen tissues, leading to a decrease in the proportion of Treg cells. It blocked the TGF-β/Smads pathway by downregulating TGF-β1, upregulating Smad4/Smad7, and inhibiting Smad2/3 phosphorylation. Cell-based experiments confirmed that WFEA-containing serum inhibited the differentiation of CD4⁺ T cells into Tregs, an effect enhanced by TGF-β1 interference. Molecular docking analyses revealed that the active components emodin and quercetin directly bound to TGF-β1 with binding energies of -5.4 kcal/mol and -5.1 kcal/mol, respectively.

WFEA could serve as a new adjunct treatment for lung cancer; however, further clinical trials are required to evaluate its long-term safety and effectiveness across various treatment stages.

WFEA may regulate the growth of Tregs to modulate the immune microenvironment of the LLC model mice, indicating its potential as an anti-LLC agent.

Schizophrenia is a heterogeneous chronic brain disorder driven by multiple pathophysiological processes. While dopaminergic theories dominate current therapies, emerging evidence highlights glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDAR) hypofunction, as a key mechanism alongside dopaminergic, serotonergic, and neurodevelopmental pathways. This article synthesizes mechanistic insights, focusing on neurotransmitter disruptions, oxidative stress, neuroinflammation, and Wnt signaling, to elucidate the clinical diversity of schizophrenia and identify biomarkers for precise diagnostics and therapeutics.

A comprehensive literature search was conducted using Web of Science, Scopus, Google Scholar, and PubMed, with keywords including “schizophrenia,” “psychosis,” “pathophysiology,” “mechanism,” and “biomarker.” Studies were selected to explore NMDAR hypofunction, glutamatergic dysregulation, and associated signaling pathways, integrating preclinical and human data to map circuit-based interactions and biomarker profiles.

We present a novel circuit-based model of schizophrenia pathophysiology, centered on NMDAR hypofunction and glutamatergic dysregulation, integrating dopaminergic, GABAergic, and inflammatory pathways. Key biomarkers, including inflammatory (e.g., high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), neurochemical (e.g., brain-derived neurotrophic factor [BDNF]), and functional (e.g., mismatch negativity [MMN]), are categorized by symptomatic domains and clinical stages, providing diagnostic and prognostic insights.

The findings underscore NMDAR hypofunction’s role in driving schizophrenia’s symptomatic spectrum, though its interplay with other pathways highlights the disorder’s complexity. Neuronal loss, although not universal, is context-specific (e.g., hippocampal interneurons), complementing functional biomarkers such as MMN. Limitations include the need for robust human validation of biomarkers and broader exploration of non-glutamatergic mechanisms.

Considering the multifaceted nature of the disorder, our emphasis on the NMDAR hypofunction model can help explain many of the synergies involved among the seemingly independent dysregulated events.

The present study is based on the most recent and extensive research on the Thiazolidine structure in the fields of organic synthesis and biological activities from 2015 to 2024, as well as the most widely used methodologies in recent years.

The three methods described in this review for the synthesis of thioazolidine derivatives are the most commonly used in recent decades and have given rise to interesting biological activities and the promotion of compounds with chemical and biological significance.

The synthesis of compounds with a thiazolidine skeleton plays a vital and interesting role in organic chemistry, with methods that are becoming increasingly sophisticated and easy to use, making it possible to obtain derivatives of biological and pharmacological importance, and a basis for future research.

The thiazolidine scaffold provides an efficient synthetic route for constructing complex molecular structures with significant biological activities. Their versatile reactivity makes them particularly interesting in organic chemistry, as well as biochemistry and pharmacology.

Oroidins are marine-derived alkaloids known for their structural complexity and a broad range of pharmacological activities. This review aims to explore their emerging role as promising scaffolds in medicinal chemistry, particularly focusing on their unique chemical structure, diverse biological effects, and recent synthetic advancements.

An extensive literature review was conducted to analyze peer-reviewed articles on the isolation, synthesis, structural characterization, and pharmacological evaluation of oroidins and their derivatives. The review highlights significant developments in synthetic strategies, including the incorporation of pyrrole carboxamide units, isotopic labeling approaches, and palladium-catalyzed reactions.

Oroidins exhibit a wide spectrum of biological activities, including antibacterial, antiviral, antimalarial, antiprotozoal, anticancer, anti-inflammatory, neurotropic, and antimuscarinic properties. Their characteristic pyrrole-imidazole core, containing a glycocyamidine moiety and azepinone ring, has been instrumental in targeting key biological pathways such as kinases, NF-κB, and the Raf/MEK-1/MAPK cascade. Structural modifications have led to enhanced potency and specificity of oroidin-based compounds.

The findings emphasize the potential of oroidins as lead compounds in drug development. Their structural diversity, bioactivity profile, and ability to inhibit critical cellular targets position them as attractive templates for therapeutic design. However, further research is needed to optimize their pharmacokinetic properties and evaluate their clinical relevance.

Oroidins represent a valuable class of marine alkaloids with significant therapeutic promise. Advances in synthetic methodologies have expanded their applicability in drug discovery, supporting continued exploration of these compounds for the development of novel therapeutic agents.