Mini reviews in medicinal chemistry最新文献

Although there have been significant advancements in cancer treatment, resistance and recurrence in patients make it one of the leading causes of death worldwide. 5-fluorouracil (5-FU), an antimetabolite agent, is widely used in treating a broad range of human malignancies. The cytotoxic effects of 5-FU are mediated by the inhibition of thymidylate synthase (TYMS/TS), resulting in the suppression of essential biosynthetic activity, as well as the misincorporation of its metabolites into RNA and DNA. Despite its huge benefits in cancer therapy, the application of 5-FU in the clinic is restricted due to the occurrence of drug resistance. MicroRNAs (miRNAs) are small, non-coding RNAs that act as negative regulators in many gene expression processes. Research has shown that changes in miRNA play a role in cancer progression and drug resistance. This review examines the role of miRNAs in 5-FU drug resistance in cancers.

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and functions. Excitotoxicity, characterized by calcium overload, plays a critical role in the pathophysiology of these disorders. In this review article, we explore the involvement of calcium dysregulation in neurodegeneration and neurodegenerative disorders. A promising therapeutic strategy to counter calcium dysregulation involves the use of calcium modulators, particularly polycyclic cage compounds. These compounds, structurally related to amantadine and memantine, exhibit neuroprotective properties by attenuating calcium influx into neuronal cells. Notably, the pentacycloundecylamine NGP1-01, a cage-like structure, has shown efficacy in inhibiting both N-methyl-D-aspartate (NMDA) receptors and voltage- gated calcium channels (VGCCs), making it a potential candidate for neuroprotection against excitotoxic-induced neurodegenerative disorders. The structure-activity relationship of polycyclic cage compounds is discussed in detail, highlighting their calcium-inhibitory activities. Various closed, open, and rearranged cage compounds have demonstrated inhibitory effects on calcium influx through NMDA receptors and VGCCs. Additionally, these compounds have exhibited neuroprotective properties, including free radical scavenging, attenuation of neurotoxicities, and reduction of neuroinflammation. Although the calcium modulatory activities of polycyclic cage compounds have been extensively studied, apart from amantadine and memantine, none have undergone clinical trials. Further in vitro and in vivo studies and subsequent clinical trials are required to establish the efficacy and safety of these compounds. The development of polycyclic cages as potential multifunctional agents for treating complex neurodegenerative diseases holds great promise.

Wounds provide a favourable site for microbial infection. Wound infection makes the healing more complex and does not proceed in an orchestrated manner leading to the chronic wound. Clinically infected wounds require proper antimicrobial therapy. Broad-spectrum antibiotics are usually prescribed first before going to targeted therapy. The current conventional mode of therapy mainly depends on the use of antibiotics topically or systemically. Repeated and prolonged use of antibiotics, however, leads to multidrug resistance. Staphylococcus aureus is the most common multidrugresistant microorganism found in wounds. It effectively colonizes the wound and produces many toxins, thereby reducing the host immune response and causing recurrent infection, thus making the wound more complex. The overexpression of efflux pumps is one of the major reasons for the emergence of multidrug resistance. Inhibition of efflux pumps is, therefore, a potential strategy to reverse this resistance. The effective therapy to overcome this antibiotic resistance is to use combination therapy, namely the combination of an inhibitor, and a non-antibiotic compound with an antibiotic for their dual function. Many synthetic efflux pump inhibitors to treat wound infections are still under clinical trials. In this connection, several investigations have been carried out on plant-based natural products as multidrug resistance-modifying agents as they are believed to be safe, inexpensive and suitable for chronic wound infections.

The thiazole ring is naturally occurring and is primarily found in marine and microbial sources. It has been identified in various compounds such as peptides, vitamins (thiamine), alkaloids, epothilone, and chlorophyll. Thiazole-containing compounds are widely recognized for their antibacterial, antifungal, anti-inflammatory, antimalarial, antitubercular, antidiabetic, antioxidant, anticonvulsant, anticancer, and cardiovascular activities. The objective of this review is to present recent advancements in the discovery of biologically active thiazole derivatives, including their synthetic methods and biological effects. This review comprehensively discusses the synthesis methods of thiazole and its corresponding biological activities within a specific timeframe, from 2017 until the conclusion of 2022.

Thrombin is a crucial enzyme involved in blood coagulation, essential for maintaining circulatory system integrity and preventing excessive bleeding. However, thrombin is also implicated in pathological conditions such as thrombosis and cancer. Despite the application of various experimental techniques, including X-ray crystallography, NMR spectroscopy, and HDXMS, none of these methods can precisely detect thrombin's dynamics and conformational ensembles at high spatial and temporal resolution. Fortunately, molecular dynamics (MD) simulation, a computational technique that allows the investigation of molecular functions and dynamics in atomic detail, can be used to explore thrombin behavior. This review summarizes recent MD simulation studies on thrombin and its interactions with other biomolecules. Specifically, the 17 studies discussed here provide insights into thrombin's switch between 'slow' and 'fast' forms, active and inactive forms, the role of Na⁺ binding, the effects of light chain mutation, and thrombin's interactions with other biomolecules. The findings of these studies have significant implications for developing new therapies for thrombosis and cancer. By understanding thrombin's complex behavior, researchers can design more effective drugs and treatments that target thrombin.

Probiotics are living microorganisms that are present in cultured milk and fermented food. Fermented foods are a rich source for the isolation of probiotics. They are known as good bacteria. They have various beneficial effects on human health including antihypertensive effects, antihypercholesterolemic effects, prevention of bowel disease, and improving the immune system. Microorganisms including bacteria, yeast, and mold are used as probiotics but the major microorganisms that are used as probiotics are bacteria from the genus Lactobacillus, Lactococcus, Streptococcus, and Bifidobacterium. Probiotics are beneficial in the prevention of harmful effects. Recently, the use of probiotics for the treatment of various oral and skin diseases has also gained significant attention. Clinical studies indicate that the usage of probiotics can alter gut microbiota composition and provoke immune modulation in a host. Due to their various health benefits, probiotics are attaining more interest as a substitute for antibiotics or anti-inflammatory drugs leading to the growth of the probiotic market.

Background: Flavonoids are a widespread category of naturally occurring polyphenols distinguished by the flavan nucleus in plant-based foods and beverages, known for their various health benefits. Studies have suggested that consuming 150-500 mg of flavonoids daily is beneficial for health. Recent studies suggest that flavonoids are involved in maintaining mitochondrial activity and preventing impairment of mitochondrial dynamics by oxidative stress.

Objective: This review emphasized the significance of studying the impact of flavonoids on mitochondrial dynamics, oxidative stress, and inflammatory response.

Methods: This review analysed and summarised the findings related to the impact of flavonoids on mitochondria from publicly available search engines namely Pubmed, Scopus, and Web of Science.

Description: Any disruption in mitochondrial dynamics can contribute to cellular dysfunction and diseases, including cancer, cardiac conditions, and neurodegeneration. Flavonoids have been shown to modulate mitochondrial dynamics by regulating protein expression involved in fission and fusion events. Furthermore, flavonoids exhibit potent antioxidant properties by lowering the production of ROS and boosting the performance of antioxidant enzymes. Persistent inflammation is a characteristic of many different disorders. This is because flavonoids also alter the inflammatory response by controlling the expression of numerous cytokines and chemokines involved in the inflammatory process. Flavonoids exhibit an impressive array of significant health effects, making them an effective therapeutic agent for managing various disorders. Further this review summarised available mechanisms underlying flavonoids' actions on mitochondrial dynamics and oxidative stress to recognize the optimal dose and duration of flavonoid intake for therapeutic purposes.

Conclusion: This review may provide a solid foundation for developing targeted therapeutic interventions utilizing flavonoids, ultimately benefiting individuals afflicted with various disorders.

Background: Synthetic cannabinoid receptor agonists (SCRAs) are the most diverse class of new psychoactive substances worldwide, with approximately 300 unique SCRAs identified to date. While the use of this class of drug is not particularly prevalent, SCRAs are associated with several deaths every year due to their severe toxicity.

Methods: A thorough examination of the literature identified 15 new SCRAs with a significant clinical impact between 2015 and 2021.

Results: These 15 SCRAs have been implicated in 154 hospitalizations and 209 deaths across the US, Europe, Asia, and Australasia during this time period.

Conclusion: This narrative review provides pharmacodynamic, pharmacokinetic, and toxicologic data for SCRAs as a drug class, including an in-depth review of known pharmacological properties of 15 recently identified and emerging SCRAs for the benefit of researchers, policy makers, and clinicians who wish to be informed of developments in this field.

Background: Interstitial Lung Diseases (ILDs) are characterized by shortness of breath caused by alveolar wall inflammation and/or fibrosis.

Objective: Our review aims to study the depth of various variants of ILD, diagnostic procedures, pathophysiology, molecular dysfunction and regulation, subject and objective assessment techniques, pharmacological intervention, exercise training and various modes of delivery for rehabilitation.

Method: Articles are reviewed from PubMed and Scopus and search engines.

Results: ILD is a rapidly progressing disease with a high mortality rate. Each variant has its own set of causal agents and expression patterns. Patients often find it challenging to self-manage due to persistent symptoms and a rapid rate of worsening. The present review elaborated on the pathophysiology, risk factors, molecular mechanisms, diagnostics, and therapeutic approaches for ILD will guide future requirements in the quest for innovative and tailored ILD therapies at the molecular and cellular levels.

Conclusion: The review highlights the rationale for conventional and novel therapeutic approaches for better management of ILD.