Mini Reviews in Medicinal Chemistry - Online First

As the main fermentation product of Aspergillus fumigatus (A. fumigatus), fumagillin is directly related to the gene of A. fumigatus and exhibits a variety of biological activities. However, its clinical application is limited by low yield and toxicity. It is of great significance to improve the yield and safety of fumagillin using A. fumigatus. Currently, research on fumagillin at home and abroad primarily focuses on a single direction and lacks a systematic review of its biosynthesis, structure-activity relationship, and strain modification technology, as well as a comprehensive theoretical framework. This study systematically reviews the biosynthesis mechanism, activity characteristics, and targeted strain modification technology of fumagillin, providing theoretical support for breakthroughs in production, toxicity regulation, and clinical transformation of fumagillin.

Three-dimensional (3D) printing is a transformative technology that has significantly influenced multiple sectors, including aviation, defence, architecture, and, more recently, healthcare and pharmaceuticals. Despite its growing adoption, there remain gaps in consolidated knowledge regarding its material versatility, regulatory considerations, and real-world implementation in clinical and pharmaceutical settings. Challenges related to biocompatibility, scalability, and the standardization of printed products hinder its full integration into medical practice. Addressing these issues requires a comprehensive understanding of the technological foundation, materials, and evolving applications of 3D printing in medicine. This review aims to provide an in-depth analysis of current advances, limitations, and prospects of 3D printing in healthcare. A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases, focusing on peer-reviewed articles published between 2010 and 2024. The review highlights key fabrication techniques, material innovations, clinical applications, and integration with emerging technologies, addressing critical challenges and opportunities for advancing personalized medicine.

The mounting threat of antimicrobial resistance has intensified the global search for novel antibacterial agents, and chalcones - the aromatic ketones characterized by an α, β-unsaturated carbonyl system has emerged as promising scaffolds against the threat of antimicrobial resistance. This review presents a detailed exploration of chalcones as potent antibacterial agents, emphasizing their structural versatility, mechanisms of action, and therapeutic potential. With a modular backbone that supports diverse substitutions and heterocyclic extensions, chalcones can be easily synthesized and chemically optimized to target a broad spectrum of bacterial pathogens, including multidrug-resistant strains such as MRSA and VRE. Mechanistically, chalcones exert antibacterial effects through multiple pathways, like disrupting bacterial membranes, inhibiting cell wall biosynthesis, interfering with DNA replication via DNA gyrase and topoisomerase IV, and suppressing protein synthesis. Their amphipathic nature and ability to bind critical bacterial enzymes offer an advantage in circumventing classical resistance mechanisms. Structure-activity relationships and computational studies have further elucidated the influence of electron-donating and electron-withdrawing groups, positional isomerism, and heterocyclic integration on antibacterial potency. A review of recent literature underlines the efficacy of chalcone derivatives against Gram-positive and Gram-negative strains, with many compounds demonstrating promising activity, such as compound 85 with MIC 3.4 nM against Ciprofloxacin with MIC 4.7 nM. The review also highlights advancements in green synthesis, QSAR modeling, and molecular docking, which collectively facilitate the rational design of next-generation chalcone-based antibacterials. Altogether, chalcones represent a structurally simple yet biologically robust class of compounds, offering significant promise as adaptable and effective agents in the evolving landscape of antimicrobial therapy.

Ruthenium complexes stand out as an excellent alternative in the field of organometallic chemistry with applications in various areas. Recently, in cardiovascular pharmacology, there has been a growing interest in investigating complexes that modulate the Nitric Oxide (NO) pathway without necessarily and directly donating NO. NO has a proven vasodilatory and cardioprotective effect, and it is known that reduced levels are associated with an increased risk of CardioVascular Diseases (CVD). Studies suggest that ruthenium complexes significantly contribute to the treatment of CVD pathophysiology through different pharmacological mechanisms, including the precise delivery of carbon monoxide (CO) to the molecular target, the release of nitric oxide species under visible and invisible (UV) light, the ability to stimulate the activation of soluble Guanylate Cyclase (sGC) enzyme, participation in the opening of potassium channels, and reduction of cytoplasmic calcium levels. This study aims to conduct a narrative review of the cardiovascular effects of ruthenium complexes, focusing on hypertension and myocardial injury, and demonstrate that metal complexes acting on the NO pathway may have promising targets for the development of therapeutic strategies in CVD treatment.

Cardiovascular diseases are the leading cause of death worldwide. Despite the development of a wide variety of drugs, treatment regimens do not seem to be able to prevent the progression of these pathologies. In recent years, the study of epigenetic mechanisms has led to the discovery of new targets that may facilitate the search for therapeutic alternatives. Furthermore, it has been demonstrated that the onset of cardiovascular diseases is associated with changes in DNA methylation status and altered histone modification patterns. Therefore, the use of natural and synthetic inhibitors of epigenetic modulators, such as DNA methyltransferases (DNMTs), is likely to constitute a new approach in the therapy of cardiovascular diseases. In this review article, we discuss the mechanisms of action of inhibitors of epigenetic modulators and their applications in the treatment of cardiovascular diseases.

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.