Current Topics in Medicinal Chemistry - Volume 25, Issue 23, 2025

Cancer and neurological diseases are among the major causes of mortality and disabilities around the world. Neurological diseases are accounting for 12% of all fatalities. The major challenge in treating these diseases is the effective drug delivery to the disease site, where traditional approaches fail to give satisfactory results. As nanoparticles have many major benefits over conventional drug delivery, they have become the preferred method for drug delivery.

The main objective of this review is to discuss the recent advancements and the role of nanoparticles in the effective treatment of cancer and neurodegenerative diseases.

Properties of nanoparticles, such as size, shape, and surface, utilized in medical therapy showed a promising impact on the efficacy of nano-drug transportation and, as a result, therapeutic efficiency. Many potentially helpful drugs for neurological disorders cannot enter the brain in therapeutic concentrations because of the blood-brain barrier, while nanoparticles can pass through it because of their size-specific properties. Besides contributing to bioavailability and half-life, nanoparticle surface properties are also important.

The use of nanotechnology in medicine has demonstrated its importance in the field of medicine and led to the development of novel therapeutic alternatives for neurological disorders and cancer. The various types of nanoparticles, like liposomes, polymeric micelle, solid nanoparticles, quantum dots, and nanogels, have shown promising results in in-vitro models and clinical investigations.

This review provides a concise description of the recent implications of various nanoparticles for the treatment of cancer and neurodegenerative disorders. It also helps in concise discussion of future opportunities of applications and challenges related to the production, efficacy, and safety of nanoparticles.

Colorectal cancer (CRC), the world's third leading cause of death, can be caused by a variety of reasons, one of which is a valine-to-glutamate mutation at position 600 in the BRAF gene. Nonetheless, the prognosis of patients with BRAF mutations remains poor, necessitating additional research in this field.

This work aims to recognize and validate innovative and effective BRAF inhibitor.

A merged-featured ligand-based pharmacophore model was validated and screened against various external databases. The pharmacokinetic and toxicological characteristics of the 102 hits were analyzed, and the appropriate ligands were docked against BRAF protein. The top four protein-ligand complexes with the lowest binding energies were chosen, and their Molecular Dynamic (MD) simulation studies were accomplished.

The finest complex selected has a Root Mean Square Deviation (RMSD) value of 2.229A° and a Radius of Gyration (RoG) value of 25.770A°. The LC50 of the best ligand was experimentally calculated to be 102.83 µg/ml. The ligand was found to destroy CRC cells, but it did not affect normal non-cancerous cells much.

This work thus proposes 3-(6,7-dimethoxy-3,4-dihydroisoquinoline-2-carbonyl)-N-(2-methoxyphenyl)benzenesulphonamide as a potential BRAF V600E inhibitor for the CRC treatment.

Jieyu Fuwei Powder (JFP) is a modified prescription of traditional Chinede medicine used to treat functional dyspepsia (FD). However, its components and how it works are still unknown. Identifying the active ingredients of JFP and understanding its therapeutic mechanism for FD were the objectives of the study.

The compounds present in JFP were analyzed using the UPLC-Q-TOF-MS/MS technique. Potential targets for compounds and diseases were obtained from Swiss Target Prediction and GeneCards databases. A PPI network was created using the STRING database to identify key targets. The Metascape database was utilized for conducting GO and KEGG pathway enrichment analyses. Molecular docking identified active compound-target interactions, validated by FD zebrafish models.

In total, 65 compounds were identified from JFP and the key active ingredients were Tangeretin, Obovatol, Magnolignan C, Magnolol, Randaiol, Magnolignan A, Luteolin, and Naringenin. The PPI network was constructed, identifying five core targets: SRC, STAT3, PIK3R1, PIK3CA, and MAPK3. JFP primarily regulates anti-depression, promotes gastrointestinal peristalsis, and influences inflammation, according to the enrichment analysis of GO and KEGG pathways. The molecular docking results indicated a strong binding affinity between these five targets and their corresponding compounds. Therefore, the MAPK and PI3K-Akt signaling pathways are important in JFP's effects on FD pathology. Experiments using the zebrafish model confirmed that JFP and its main components could enhance gastrointestinal motility, thus demonstrating the effectiveness of the network pharmacology screening strategy.

The study revealed the active ingredients and mechanisms of JFP in treating FD, supporting its clinical application.

2.5% of adults worldwide suffer from hyperthyroidism, which is associated with osteoporosis, heart disease, and increased mortality.

The current study evaluates the protective and therapeutic effect of Ovothiol A on Thyroxine-induced hyperthyroidism in rats.

Experimental animals were split into two categories: protective and curative. Each group was further separated into three subgroups (6 per group): control, hyperthyroidism (HT), and Ovothiol-A (250 mg/kg). Thyroxine hormone (600 mg/kg) is administered orally to rats to induce HT.

Ovothiol-A supplementation resulted in significant decreases in organ weight index, T3, T3,T4, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, malondialdehyde, nitric oxide levels, and tumour necrosis factor-alpha while increasing in body weight, TSH, glutathione reduced, catalase, and glutathione-S-transferase levels. Histopathological investigation revealed significant thyroid and liver tissue improvements, significantly reducing collagen deposition.

Ovothiol-A exhibited protective and therapeutic effects against hyperthyroidism in rats. Ovothiol-A exhibits antithyroid activity by stimulating the antioxidant system, reducing inflammation, and restoring thyroid hormone levels.