Pharmaceuticals

Objectives: Combining two pharmacophores into one molecule with multiple applications presents interest in the field of medicinal chemistry. Quinazolinones are among privileged scaffolds due to their wide biological activities, whereas hydrazones are versatile linkers with pharmacological potential. Thus, this article focused on a green method for the synthesis of new N-acyl-hydrazones of 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide and the exploration of their biological potential. Methods: The novel N-acyl-hydrazones (1a–1f) were synthesized under microwave irradiation, using various substituted salicylaldehydes and benzaldehydes. The products were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and HRMS. Their pharmacological profile was assessed by in silico methods and docking simulations. Biological evaluation included antioxidant, antimicrobial, and cytotoxic activities, as well as preliminary toxicity on Artemia franciscana. Results: Spectroscopic data indicated syn-E and anti-E isomers. Compound 1c showed the highest antioxidant activity. Antimicrobial assays indicated narrow-spectrum activity, with compounds 1a and 1b being most effective against C. albicans and S. aureus. Biofilm inhibition assays revealed that 1a and 1c interfered with microbial adhesion, highlighting their potential in combating biofilm-associated infections. Cytotoxicity tests on HT-29 and A431 cancer cell lines showed selective anticancer effects for compounds 1a–1d, with minimal toxicity on normal Vero cells, especially for 1b and 1d. Toxicity against Artemia franciscana correlated with in vitro cytotoxicity data, revealing low lethality for all N-acyl-hydrazones. Docking studies indicate that the antibacterial activity may involve inhibition of S. aureus DNA gyrase B, whereas the cytotoxic effects could be mediated by interaction with the EGFR kinase. Conclusions: These findings may increase the chances of identifying a lead compound in this class, supporting the further development of selected N-acyl-hydrazones and their pharmacological exploration.

Drug discovery is a complex and multi-stage process that requires advanced analytical technologies capable of accelerating preclinical evaluation and improving the precision of therapeutic design. The combination of fluorescence and magnetic resonance imaging (MRI) within multimodal imaging plays an increasingly important role in modern pharmacokinetics, integrating the high molecular sensitivity of fluorescence with the non-invasive anatomical visualization offered by MRI. Fluorescence enables real-time monitoring of cellular processes, including drug–target interactions and molecular dynamics, whereas MRI provides detailed structural information on tissues without exposure to ionizing radiation. Hybrid probes—such as superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with near-infrared (NIR) fluorophores or gadolinium-based complexes linked to optical dyes—enable simultaneous acquisition of molecular and anatomical data in a single examination. These multimodal systems are being explored in oncology, neurology, and cardiology, where they support improved visualization of tumor biology, amyloid pathology, and inflammatory processes in vascular disease. Although multimodal imaging shows great promise for enhancing pharmacokinetic and pharmacodynamic studies, several challenges remain, including the potential toxicity of heavy-metal-based contrast agents, limited tissue penetration of fluorescence signals, probe stability in vivo, and the complexity and cost of synthesis. Advances in nanotechnology, particularly biodegradable carriers and manganese-based MRI contrasts, together with the integration of artificial intelligence algorithms, are helping to address these limitations. In the future, fluorescence–MRI hybrid imaging may become an important tool in personalized medicine, supporting more precise therapy planning and reducing the likelihood of clinical failure.

Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies.