Mini Reviews in Medicinal Chemistry - Online First

Individuals diagnosed with inflammatory bowel disease (IBD) face a significantly heightened risk of developing colorectal cancer (CRC), primarily due to persistent intestinal inflammation that fosters neoplastic transformations across the colon. This narrative review delves into the potential of certain fruits, such as black raspberries, Amazonian açaí, apples, grapes, cocoa, Ziziphus jujuba, and Moringa oleifera, in mitigating IBD-induced CRC. Preclinical studies indicate that these fruits possess anti-inflammatory and antioxidant properties that may disrupt carcinogenic pathways. Notably, black raspberries have demonstrated the ability to modulate epigenetic markers by demethylating tumor suppressor genes and inhibiting DNA methyltransferases (DNMT), like DNMT1 and DNMT3B. This epigenetic modulation influences the Wnt signaling pathway, crucial in CRC development, and affects cellular processes, such as proliferation, apoptosis, and angiogenesis. Animal models further support these findings, showing that black raspberries can suppress β-catenin signaling, reduce chronic inflammation, and decrease tumor incidence. This comprehensive analysis underscores the promising role of specific fruits in CRC prevention among IBD patients and highlights the need for further research to translate these findings into clinical applications, potentially benefiting both public health and the nutraceutical industry.

Breast cancer is a heterogeneous disease consisting of several molecular subtypes, such as Hormone Receptor-positive (HR+), Human Epidermal Growth Factor Receptor 2-positive (HER2+), and Triple-Negative Breast Cancer (TNBC). Although a lot of success has been realized in targeted agents, there still remain significant problems, including resistance to drugs, toxicity related to treatment, and few therapeutic possibilities for aggressive subtypes. Confronting such limitations requires complementary treatment approaches with better efficacy and safety profiles. Phytoconstituents from natural sources have emerged as potential therapeutic agents due to their multitargeting activity, good safety profile, and capacity to evade drug resistance. These bioactive molecules, such as flavonoids, alkaloids, terpenoids, and saponins, possess various mechanisms of action, including modulation of cell cycle regulators, induction of apoptosis, inhibition of angiogenesis, suppression of metastasis, and regulation of critical oncogenic signaling pathways. Their interference with several cancer pathways gives them a holistic strategy for breast cancer therapy. This review offers an in-depth examination of new phytoconstituents that target the molecular basis of various subtypes of breast cancer. It also highlights their scope for integration into traditional paradigms either as monotherapy or in combination with current therapies to increase therapeutic impact with the least adverse effects. Through the clarification of their mechanisms of action and therapeutic advantages, this review promotes the ongoing pursuit of phytoconstituents as potential contenders in contemporary oncology, providing novel targets for the control of breast cancer and enhanced patient care.

Musculin antisense RNA 1 (MSC-AS1) is a long non-coding RNA (lncRNA) located on human chromosome 8q13.3-q21.11. Emerging evidence shows that MSC-AS1 is either upregulated or downregulated in 16 types of human cancers, and is associated with clinical pathological features and patient prognosis in 12 of these cancers. It is widely believed that the dysregulation of MSC-AS1 contributes to tumor cell growth, metastasis, epithelial-mesenchymal transition (EMT) progression, metabolic reprogramming, and drug resistance formation. Mechanistically, MSC-AS1 can act as a competing endogenous RNA (ceRNA) by sponging 14 miRNAs to affect the expression of downstream mRNAs, or it may directly interact with proteins, both of which contribute to the activation of the PI3K/AKT and Wnt/β-catenin signaling pathways. Our review study suggests that MSC-AS1 is a potential cancer biomarker and therapeutic target. In summary, we have explained the research on MSC-AS1 related to cancer treatment, its expression patterns, functional characteristics, and molecular mechanisms in malignant tumors. We have further emphasized its significance in clinical prognosis and therapeutic applications.

Quinoxalines are a versatile class of nitrogen-containing heterocyclic compounds that have been extensively studied for their diverse pharmacological properties. Recently, interest has grown in exploring quinoxaline derivatives for applications in oral health, driven by their unique mechanisms of action and potential to address major challenges in dental medicine. This review comprehensively examines the recent progress in the development of quinoxaline-based compounds targeting oral pathogens responsible for dental caries, periodontitis, and other biofilm-associated diseases. Beyond their antimicrobial effects, quinoxalines also exhibit anti-inflammatory properties by modulating key molecular pathways implicated in periodontal inflammation, thereby offering a dual therapeutic potential. Moreover, their incorporation as functional additives in restorative dental materials is emerging, aiming to enhance antimicrobial efficacy and improve material performance. Despite promising in vitro and in vivo data, several critical barriers must be overcome before clinical translation can be realized. These include ensuring biocompatibility with oral tissues, achieving formulation stability under the dynamic conditions within the oral environment, and optimizing delivery systems to ensure targeted, sustained release at the site of action. This review highlights current strategies to address these challenges and proposes directions for future research, including advanced formulation technologies and comprehensive preclinical evaluations. Ultimately, quinoxaline derivatives hold significant promise as multifunctional agents capable of integrating antimicrobial, anti-inflammatory, and biomaterial-enhancing properties to improve oral health outcomes. This synthesis of current knowledge supports continued investigation into quinoxalines as novel therapeutics and functional components for dental care.

Medical diagnostics, environmental monitoring, and food safety are key domains being transformed by the ongoing revolution in optical biosensors. These light sensors are highly sensitive and specific for detecting specific biological interactions, allowing for real-time, label-free detection. Biorecognition elements (such as enzymes, antibodies, or nucleic acids), following interaction with the target analyte, generate optical signals based on the same key principles as optical biosensors. Surface plasmon resonance (SPR), fluorescence-based sensors, and fiber optic sensors offer a wide range of biosensors capable of detecting a broad spectrum of biological and chemical agents at trace concentrations. Diagnostic capability has become efficient and rapid with advances in nanotechnology and microelectronics, particularly in nanopores. Monitoring of cardiovascular health using wearable optical biosensors, such as photoplethysmography (PPG), is a non-invasive method. It has also been recently improved to better track heart rate and blood pressure, as well as evaluate mental and vascular health. Wearable optical biosensors support technologies, such as continuous monitoring and early detection of anomalies, which help in personalized healthcare. Optical biosensors are particularly suitable for detecting pathogens, biomarkers, and pollutants in clinical settings, as well as for environmental monitoring and food safety assessments. These applications range from biopharmaceuticals to biotechnology and personalized care, which are used to monitor diseases, discover drugs, and detect pathogens. Despite progress, matrix interference with the sample matrix, sensor stability, and miniaturization remain challenges to be overcome. However, with future progress in materials science, nanotechnology, and increased integration with the Internet of Things (IoT), the potential for optical biosensors will continue to rise as portable, cost-effective, real-time data-analyzing diagnostic tools that expand accessibility to those in underserved regions. Developed using optical and electrochemical approaches, the biosensors reviewed in this article are discussed in terms of their principles, types, applications, and prospects, including their roles in healthcare and environmental sectors.

The urinary tract (UT) was once considered sterile, but now it is known to host a diverse community of microorganisms, known as the urinary microbiome. The collective microbiota is made up of bacteria, fungi, and viruses, necessary for maintaining UT health. This review aims to synthesize current knowledge on the urinary microbiome and clarify its emerging role as a key modulator in both health and a wide spectrum of UT disorders. Dysbiosis within this microbial community has been linked to conditions such as urinary tract infections (UTIs), interstitial cystitis/bladder pain syndrome (IC/BPS), urinary incontinence, urolithiasis, benign prostatic hyperplasia (BPH), and even urinary tract malignancies. Advances in methodologies, such as expanded quantitative urine culture and metagenomics, have provided valuable insights into microbial variability influenced by factors like age, sex, and disease conditions. Additionally, this review explores the therapeutic potential of probiotics and bacteriophages, as well as the association of urinary microbiota with autoimmune and inflammatory conditions. Special emphasis is placed on translational relevance, including emerging microbiome-targeted therapies and personalized interventions for UTIs. Ethical considerations allied with UT microbiome research, such as data privacy, informed consent, and equitable access to emerging therapies, are also discussed. Despite substantial progress, challenges such as methodological heterogeneity, a lack of longitudinal data, and unresolved causal relationships persist. The study concludes by identifying key knowledge gaps and proposing future directions for multidisciplinary research to advance therapeutic innovation in urological health.

aThe growing prevalence of multidrug resistance and its detrimental effects pose a significant threat to public health, which is one reason for the current interest in the introduction of novel agents. To combat this adverse effect and drug resistance, numerous drugs have been developed over time, and their safety is still being evaluated; derivatives or medications based on the carbazole moiety are one of the key contributors. Therefore, this review explores carbazole-based derivatives as possible drugs to treat Alzheimer's, diabetes, inflammation, cancer, and many more, along with their synthetic schemes, SARs, and activity. Some of the carbazole-based drugs available in the market and under clinical trials are also tabulated. By integrating this insight, describe how these compounds are being reinvented as targeted therapeutic agents. This comprehensive analysis is designed to guide researchers in developing next-generation drugs to address various challenges and leverage the unique pharmacological properties of carbazole-derived drugs.

Arthritis has become a global public health issue due to its diverse risk factors and high prevalence. Therefore, there is a demand for more effective drugs to improve these situations. Triterpenoids have attracted the interest of researchers because of their broad spectrum of biological activities and pharmacological effects. The aim of this review is to provide an updated overview of the potential of triterpenoids and of their derivatives as therapeutic agents against Rheumatoid Arthritis (RA) and Osteoarthritis (OA), based on their anti-inflammatory and immunomodulatory properties. This review discusses the chemical and pharmacological properties of triterpenoids and their derivatives, focusing on the different mechanisms by which this class of compounds achieves therapeutic benefits in arthritis. The conclusions indicate that triterpenoids and their derivatives have a favorable potential therapeutic effect on arthritis.

Recent trends have shown the development of various medicinally important compounds that specifically target B-cell receptor (BCR) pathways at various segments that have a major role in Bruton’s tyrosine kinase (BTK) receptor, which belongs to the family of kinases. These kinases are usually situated close to the cell membrane due to which they participate in upstream processing of BCR signalling. Various molecules have been potentialized to target these signalling pathways of these kinase receptors in order to achieve a pharmacological effect. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of multiple diseases. BTK inhibitors work by regulating B-cell receptor signalling along with inflammatory pathways and immune cell interactions, offering more advanced treatment options compared to traditional therapies. In addition to BTK inhibitors, an extensive knowledge of the pharmacological mechanisms underlying the blockage of these receptors is necessary in order to more accurately forecast when and where a patient could need combination therapy or just one medication. Efforts have been made to facilitate translational discoveries, drug re-purposing concepts, and further development of precision medicine products. This thorough literature study has focused on studies published until June 2025.

Intracellular calcium (Ca²⁺) levels are critical in maintaining cellular activities and are tightly regulated. Neuronal degeneration and regeneration rely on calcium-binding proteins. Calmodulin (CaM) is a calcium sensor and the primary regulator of receptors and ion channels that maintain calcium homeostasis. The calmodulin binding domains are present in proteins that serve as risk factors and biomarkers associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic Lateral Sclerosis, and other neurodegenerative diseases, suggesting calmodulin ligands as emerging therapeutic targets for treatment. Inhibiting CaM to develop new therapies has drawbacks, as CaM is a ubiquitous molecule involved in many regulatory pathways. Recently, new strategies for disrupting CaM interactions with its targets have shown promising approaches to treatment.

The structures of human CaM, its binding proteins, and inhibitors are well studied, with particular emphasis on the conservation of CaM amino acid sequences and the ability to bind protein fragments of high sequence variability, which exhibit common characteristics of amphipathic helices carrying basic amino acids.

In this review, we discuss structural characteristics of CaM and its ligands in the context of transcriptional regulation. Specific binding of CaM to (1) basic region/helix-loop-helix/leucine zipper and (2) helix-turn-helix high mobility group box containing Sox families of transcription factors highlights common features of CaM binding sequences, which suggest their regulatory functions. We describe key proteins involved in neurodegeneration and transcription factors subject to calmodulin regulation that are candidates for the development of new approaches to treating neuronal diseases.