Current topics in medicinal chemistry最新文献

Mefloquine is a synthetic antimalarial drug known for its effectiveness in the treatment and prevention of malaria. This belongs to the amino alcohol group of compounds. Its structure consists of a quinoline and piperidine ring, along with two chiral centers, which give rise to four distinct stereoisomers. There are various synthetic methods for preparing this compound from starting materials such as p-trifluoromethylaniline, 4-bromoquinoline, and trifluoroacetimidoyl iodide. In recent years, mefloquine has gained attention for its potential therapeutic applications beyond malaria, with research exploring its use in cancer therapy, parasitic infections, neurological disorders, tuberculosis, and COVID-19. This article covers its synthetic approaches, established application as an antimalarial compound, as well as repurposed therapeutic applications.

Introduction: Nitrosamines are genotoxic impurities formed from reactions between amines and nitrosating agents, which are commonly found in many consumer products and pharmaceuticals. Their presence poses serious risks due to their established carcinogenic potential, particularly with long-term exposure.

Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science to investigate the mechanisms, sources, analytical detection methods, and regulatory frameworks of nitrosamine formation. Relevant studies and guidelines were analyzed to identify risk patterns and control strategies.

Results: Nitrosamines may form during the synthesis of Active Pharmaceutical Ingredients (APIs), due to excipient contamination, or through degradation during storage. Sensitive techniques, such as LC-MS and GC-MS, enable trace-level detection. Regulatory bodies, including the FDA and EMA, have established Acceptable Intake (AI) limits and mandated risk assessments and control measures.

Discussion: Nitrosamine formation is influenced by factors, such as pH, heat, moisture, and the interaction of amines with nitrosating agents. The variability in excipient composition and manufacturing processes adds complexity to prevention efforts, underscoring the need for productspecific risk evaluation.

Conclusion: Minimizing nitrosamine contamination requires robust risk assessment, sensitive analytical techniques, and strict adherence to evolving regulatory requirements. This review highlights the importance of proactive control throughout the formulation, manufacturing, and storage stages to ensure patient safety and pharmaceutical quality.

Changes in the body's natural glucose levels have been associated with the onset of diabetes mellitus. It is frequently accompanied by a number of long-term consequences, including cardiovascular disease, retinopathy, nephropathy, and cataracts. Aldose reductase (AR), an enzyme belonging to the aldoketo reductase superfamily, plays a crucial role in the polyol pathway of glucose metabolism by converting glucose into sorbitol. Aldose reductase inhibitors (ARIs), a key target for reducing sorbitol flow through the polyol pathway, may be a new target for treating significant diabetic complications. A variety of structural classes of ARIs have been developed. These include: i) derivatives of carboxylic acids (e.g., Epalrestat, Alrestatin, Zopalrestat, Zenarestat, Ponalrestat, Lidorestat, and Tolrestat); ii) derivatives of spirohydantoins and related cyclic amides (e.g., Sorbinil, Minalrestat, and Fidarestat); and iii) phenolic derivatives (e.g., related to Benzopyran- 4-one and Chalcone). The current review article provides concise details of the various chemical classes that aldose reductase inhibitors play in the treatment of diabetic complications. This also describes the advancements made in ARI research and possible applications by obtaining the required data. The process involves thoroughly searching multiple databases-such as PubMed, ScienceDirect, and SciFinder-for citations.

Amarogentin is a secoiridoid glycoside that was initially isolated from the medicinal plant Swertia chirayita. It is well-known for its formidable bitter characteristics and the varied pharmacological actions it possesses. Especially in both conventional and modern medical practices, this molecule has garnered considerable attention due to its enormous therapeutic potential. Amarogentin possesses a wide range of biological actions, some of which include functions that are hepatoprotective, anti-inflammatory, anti-cancer, anti-diabetic, and antibacterial. The hepatoprotective function it possesses is achieved by enhancing antioxidant defense systems and reducing liver damage caused by toxins. It is believed that the ability of amarogentin to block proinflammatory mediators, such as TNF-α and IL-6, is responsible for its anti-inflammatory properties. The stimulation of apoptosis and the reduction of cancer cell proliferation in various tumor models are two additional ways in which it demonstrates promising anti-cancer potential. The antidiabetic activity of amarogentin is characterized by the modification of glucose metabolism as well as an improvement in insulin sensitivity. To enhance the therapeutic efficacy of amarogentin, further research is needed to investigate its bioavailability and stability in the human body. This is despite the fact that it possesses a wide range of pharmacological advantages. There are formulation options that could improve its pharmacokinetic profile. Some examples of these strategies are nanoparticle delivery systems and derivatization. In general, amarogentin exhibits a great deal of promise as a natural therapeutic agent for the treatment of liver diseases, cancer, and metabolic disorders. Accordingly, there is a need for further research into the mechanisms underlying its clinical applications and potential uses.

Oxidative stress plays a central role in the pathogenesis of liver diseases, including hepatotoxicity, by disrupting the balance between reactive oxygen species (ROS) and the hepatic antioxidant defense system. Excessive ROS production leads to inflammation, fibrosis, and cellular damage. Antioxidants-both endogenous and exogenous-can mitigate these effects by neutralizing ROS and restoring redox homeostasis. This review evaluates the mechanistic role of antioxidants in modulating key oxidative stress-related signaling pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), nuclear factorkappa B (NF-κB), phosphoinositide 3-kinase/Akt (PI3K/Akt), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Through the regulation of these pathways, antioxidants reduce apoptosis, suppress pro-inflammatory signaling, and enhance the expression of detoxifying enzymes. Natural compounds like flavonoids, polyphenols, and vitamins C and E have shown hepatoprotective effects, while synthetic antioxidants and their combinations with other therapeutic agents represent promising strategies for clinical application. This review underscores the therapeutic potential of antioxidants in combating oxidative stress-induced hepatotoxicity by offering a comprehensive overview of their mechanistic targets.

Introduction: Zika virus (ZIKV), a flavivirus primarily transmitted by Aedes aegypti, became a major global health concern during the 2015-2016 outbreak, particularly in Brazil. Its association with congenital malformations and neurological disorders underscores the urgent need for effective therapeutic interventions. This review explores molecular targets for ZIKV treatment within the Brazilian context.

Method: A systematic search was conducted using PubMed, ScienceDirect, and Scopus for studies published between 2004 and 2024. Inclusion criteria focused on studies identifying druggable molecular targets related to viral replication, immune evasion, or host-virus interactions. Key search terms included "Zika virus," "molecular targets," "Brazil," "antiviral," and "drug discovery."

Results: The review identified several critical viral proteins, NS1, NS3, NS5, and the envelope protein, as potential drug targets. Host cellular factors essential for viral survival were also highlighted. Technologies such as high-throughput screening, molecular docking, and structural genomics contributed significantly to the identification and validation of these targets.

Discussion: Although promising targets have been identified, therapeutic development is hindered by the genetic variability of ZIKV and its antigenic similarity to other flaviviruses, notably the dengue virus. These challenges complicate the specificity and efficacy of drugs. Nevertheless, Brazil has made strides in research infrastructure and collaborations to tackle these obstacles.

Conclusion: This review synthesizes current knowledge on ZIKV molecular targets and ongoing drug discovery efforts. The findings support the strategic development of antivirals and emphasize the necessity for sustained investment in research to mitigate future ZIKV outbreaks in Brazil and globally.

Manassantin, a dineolignan, is a natural compound that has gained significant attention due to its diverse pharmacological properties, including anti-inflammatory, anticancer, neuroprotective, and antimicrobial effects. Its unique polyphenolic scaffold offers a versatile platform for drug development, enabling targeted therapeutic applications. This review explores the molecular mechanisms underlying the bioactivity of manassantin with a focus on its role in modulating key cellular pathways, including NF-κB, MAPK, JAK/STAT, oxidative stress, apoptosis, and inflammatory signaling. Furthermore, it highlights recent advancements in structural modifications aimed at enhancing the pharmacokinetic and pharmacodynamic properties of this compound. By unlocking the full therapeutic potential of manassantin, this study paves the way for its future development as a multifunctional therapeutic agent.