Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology最新文献

2-Aminobenzothiazole's planar structure and tendency to bind to a diverse set of oncogenic targets have made 2-aminobenzothiazole a highly sought heterocyclic in research for anticancer agents. In the past 10 years, intense research in medicinal chemistry has clarified that carefully planned substitution for benzothiazole can yield highly efficient and specific anticancer agents. In this critical assessment, we will specifically evaluate both research and efforts related to 2-aminobenzothiazole-based anticancer agents between 2015 and 2024 for their anticancer targets, SAR relationship, and mechanism of action. In particular, we highlight 2-aminobenzothiazole-based compounds targeting CDKs, Aurora kinase, RAF kinase, and various receptor and non-receptor tyrosine kinases such as EGFR, VEGFR-2, CSF1R, MET, FAK, and DYRK2. Besides inhibition of kinase activity, other non-kinase targets are systematically analysed and introduced in this patent review. These include BCL-2 family members, HDACs, epigenetic modifiers (LSD1, NSD1, FTO), HSP90, mutant p53, and DNA topoisomerases. Substitutions at the C-2, C-5, C-6, and C-7 positions of the benzothiazole ring are examined thoroughly about their anticancer properties and target engagement. Also underscored are the existence of commercially available drugs and patented compounds, as well as translational candidates featuring the 2-aminobenzothiazole pharmacophore. The paper emphasises the dual mechanistic targetability of 2-aminobenzothiazole derivatives as valuable lead compounds targeting both kinases and other targets in an innovative manner aimed at future development of targeted anti-cancer therapies.

Etrasimod, a next-generation oral selective sphingosine-1-phosphate (S1P) receptor modulator, has emerged as a promising treatment for immune-mediated inflammatory diseases (IMIDs), most notably moderate-to-severe ulcerative colitis (UC). Acting primarily on S1PR1, S1PR4, and S1PR5, etrasimod effectively reduces gastrointestinal inflammation by retaining lymphocytes in lymphoid tissues, thereby minimising systemic immunosuppression and associated risks. Etrasimod provides better safety, a favorable pharmacokinetic profile, and a short washout period when compared to first-generation modulators, improving patient adherence and efficacy. Its therapeutic potential has been highlighted by clinical trials, such as the ELEVATE UC 12 and ELEVATE UC 52 studies, which showed notable improvements in clinical remission and mucosal healing when compared to placebo. With a tolerable safety profile and convenience of once-daily oral dosing, etrasimod stands out as an important advancement in the management of UC and holds further potential in other IMIDs, representing a step forward in targeted, patient-friendly immune modulation.

Autophagy, a highly conserved catabolic process, plays a fundamental role in maintaining cellular homeostasis by degrading and recycling unnecessary or dysfunctional cellular components through lysosomal pathways. It serves as a vital mechanism for clearing damaged proteins, organelles, and other cytoplasmic constituents, ensuring the cell's functional integrity, especially under stress conditions such as nutrient deprivation. Various forms of autophagy macro-autophagy, micro-autophagy, and chaperone-mediated autophagy are involved in distinct regulatory pathways that respond to different physiological and pathological stimuli. Recent research continues to uncover the molecular underpinnings and biological significance of these pathways, emphasizing their critical contributions to human health and disease.

Substituted 2-phenyl imidazolidines present a structurally diversified family of heterocycles with several medicinal potentials. Their significance is due mostly to the presence of the phenyl group at the C-2 position, which enhances lipophilicity, rigidity, electronic distribution, and molecular recognition. This review summarises the current advances in the synthesis, biological activity, mechanistic understanding, and nanocarrier-based administration of 2-phenyl imidazolidine derivatives. Amongst the most successful synthetic methodologies described are the classical cyclisation processes, condensation pathways, urea/thiourea-based procedures, green chemistry approaches, and nanocatalyst-assisted techniques. These protocols ensure that highly functionalized derivatives are easily accessible. The biological activities of phenyl imidazolidines encompass anticancer, antibacterial, anti-inflammatory, CNS-modulating, antioxidant, and enzyme-inhibitory properties. Accordingly, a mechanistic study shows these phytochemicals interact with major molecular targets like DNA, tubulin, and other enzymes, leading to cell cycle arrest, induction of apoptosis, regulation of reactive oxygen species, and enzyme inhibition. The computational techniques enhance the optimisation based on SAR through the explanation of electrical behaviour and binding interactions. Recent advances in nanotechnology have enabled the encapsulation of these derivatives within polymeric nanoparticles, lipid-based carriers, metal-doped nano-systems, and hybrid nano-structures. These platforms improve therapeutic effectiveness owing to an increase in solubility, stability, and targeted delivery. This review combines synthetic, biological, mechanistic, and formulation factors to serve as a backbone for logical drug design. It highlights the potential of 2-phenyl imidazolidines as attractive scaffolding in the development of new medicinal compounds.

Introduction: Thiazolidinedione is one of the most important classes in medicinal chemistry. Thiazolidine-2,4-dione (TZD) is a versatile scaffold, best known for its use in the development of anti-diabetic drugs such as pioglitazone and rosiglitazone. Beyond their well-established antidiabetic properties, TZDs exhibit a wide range of biological activities including anticancer, anti-inflammatory, antibacterial, and neuroprotective effects, making them potential candidates for various therapeutic applications.

Methodology: This review focuses on the complete journey of TZD derivatives-from their synthetic design to their inclusion in commercialized pharmaceutical products. Structure-activity relationship (SAR) studies were analyzed to understand how modifications in the TZD core affect binding affinity, selectivity, and therapeutic efficacy. In addition, the review consolidates findings from biological evaluations and computational studies that provide deeper insights into the mechanism of action and pharmacological potential of TZD derivatives.

Conclusion: This review highlights the significance of the TZD scaffold as a multifunctional pharmacophore in drug discovery. By integrating synthetic strategies, SAR analysis, and advanced computational tools, TZD derivatives continue to show great potential for the development of new therapeutic agents for various diseases. The combined understanding of chemistry and biological activities of TZDs paves the way for innovative research and future drug design.

Iridium therapy is changing how cancer is treated in the future. Because of their remarkable photophysics, redox sensitivity, and structural adaptability, Ir (III) complexes offer a powerful and multipurpose solution for precision oncology. These substances can be engineered to target particular Compounds organelles, photoinduced activation, and real-time imaging on a single molecular platform, which allows for simultaneous diagnosis and treatment, unlike conventional chemotherapeutics. This review highlights the recent surge in iridium complex synthesis and biomedical applications, with a focus on developments within the past five years. We address their many structural classes, including cyclometalated compounds, mononuclear Ir (III) species, and formulations based on nanoparticles, emphasizing their subcellular accumulation patterns, intracellular trafficking, and cellular uptake methods. Because iridium complexes are better at generating reactive oxygen species (ROS), causing mitochondrial damage, and fragmenting DNA, they can kill cancer cells selectively without harming healthy tissue. Novel strategies such as administration that responds to the tumor microenvironment, induction of immunogenic cell death, and combination with photothermal or radiation are propelling iridium medicines to the forefront of multimodal cancer treatment. Iridium complexes, which are distinguished by their improved pharmacokinetics and biodegradability due to clever nanocarrier engineering, have significantly lower systemic toxicity than platinum equivalents. Iridium-based platforms are powerful anticancer tools with strong translational potential that bridge biology and chemistry, imaging and therapy. This review is meant to serve as a last resort for medicinal chemists, scientists working in nanomedicine, and oncologists who want to maximize iridium's anti-cancer potential.

The discovery of ROS1 and NTRK gene fusions has transformed treatment strategies for a specific group of cancers, particularly non-small cell lung cancer (NSCLC). First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance. Taletrectinib (DS-6051b, AB-106) is an orally bioavailable, next-generation selective inhibitor of ROS1 and NTRK kinases, designed to tackle these issues. Preclinical assessments demonstrated its strong efficacy against both wild-type and resistant kinases, including the clinically challenging ROS1 G2032R mutation, alongside good CNS penetration and prolonged intracranial responses. Clinical studies, like the notable TRUST and TRUST-II trials, have demonstrated elevated objective response rates in TKI-naïve NSCLC patients (often exceeding 85-90%) and substantial effectiveness in groups pretreated with crizotinib. Basket trials are expanding their evaluation to include NTRK fusion-positive solid tumors, confirming a tumor-agnostic strategy. Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib. Regardless of these advancements, challenges remain, including the possibility of new resistance mutations, limited patient enrollment in early-phase trials, and the critical need to enhance the management of long-term toxicities. Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.

Introduction: Worldwide, heart failure remains one of the leading causes of death and morbidity. Drug-induced cardiotoxicity is a significant adverse effect on cardiovascular health and may arise from various pathogenic mechanisms. Several therapeutic agents have been associated with cardiac injury due to their interactions with cardiac receptors and pathways. Understanding these mechanisms is crucial for minimizing cardiovascular risks and improving patient safety.

Material and methods: This review systematically explores the diverse mechanisms of drug-induced cardiotoxicity by analyzing existing literature and clinical studies. It highlights the commonly implicated therapeutic agents, including lidocaine, trastuzumab, orciprenaline, azidothymidine, anthracyclines, fluoropyrimidines, NSAIDs, terodiline, digitalis, and antiviral drugs. The study also identifies major receptors involved in the pathogenic processes leading to cardiotoxicity. Furthermore, risk factors predisposing patients to cardiac damage and current strategies for early detection, monitoring, and prevention are critically reviewed to provide a comprehensive understanding of the topic.

Conclusion: A thorough understanding of drug-receptor interactions and cardiotoxic pathways is essential to reduce the incidence of drug-induced cardiac injury. Implementing multidisciplinary approaches can help minimize cardiovascular risks without compromising therapeutic efficacy. Continued research on cardioprotective interventions and early diagnostic strategies will enhance patient safety and ensure the long-term success of modern pharmacotherapy.

Background: Diabetic glaucoma is a serious eye disorder that can lead to permanent vision loss and is increasingly seen in individuals with long-term diabetes. With its rising global incidence, there is a critical need for early and reliable methods of detection to prevent severe complications.

Objective: This study highlights the growing role of artificial intelligence (AI), especially deep learning technologies, in identifying diabetic glaucoma at an early stage. It also reviews progress in bionic eye technologies designed to help restore vision in affected individuals.

Methods: Relevant scientific literature was reviewed by searching databases including PubMed, Taylor francis, ScienceDirect, MDPI, and Bentham. Articles published up to 2025 were considered, focusing on terms such as "diabetic glaucoma,""retinal imaging,""deep learning,""AI in eye care,""bionic eye,"and "neuroprosthetics."Studies were selected based on their relevance to diagnostic innovations and vision-restoration technologies.

Results: Recent developments in AI have enabled more accurate interpretation of retinal images, such as those from fundus cameras and optical coherence tomography (OCT), aiding in early detection of structural changes linked to glaucoma. At the same time, bionic eye systems-based on neuroprosthetic implants-are showing promise in partially restoring vision in cases of severe visual impairment.

Conclusion: Combining AI-powered diagnostics with emerging bionic eye technologies represents a major shift in managing diabetic glaucoma. These innovations have the potential to improve early detection and offer new options for visual rehabilitation, paving the way for more effective patient care in ophthalmology.

Resistant Hypertension is a significant clinical problem. It is found in the most of individuals who, even with the greatest multi-drug therapy, are not able to manage their blood pressure. A new dual endothelin receptor antagonist (ERA) called aprocitentan (Aprocitirom) inhibits both ETA and ETB receptors. It has emerged as a potentially useful treatment for such patients. This review article considers Aprocitentan's pharmacological profile, preclinical development, clinical efficacy, and potential. Preclinical experiments revealed that Aprocitentan possesses vasodilatory, anti-inflammatory, & anti-fibrotic activities. It is also well absorbed from the gastrointestinal tract and safe in various species. The Phase I trials reinforced that it is well tolerated and can be administered once daily. In Phase II trials, Aprocitentan induced dose-proportional reductions in systolic and diastolic blood pressure in patients with resistant hypertension. The critical Phase III PRECISION trial also validated its efficacy. It showed impressive and sustained decreases in blood pressure, with a favorable safety profile and low hepatotoxicity, and minimal fluid retention. An important step forward in the treatment of ERA has come with the FDA and EMA approval of aprocetentan in resistant hypertension. Its metabolism, which is not dependent on CYP enzymes, adds to its therapeutic applications and minimizes the likelihood of drug interactions. Subgroup analysis and further real-world studies indicate further benefits in patients with metabolic disorders and chronic kidney disease. Aprocitentan could potentially prove useful in the future for vascular disease, heart failure, and diabetic nephropathy. Clarifying its potential role in the future to treat hypertension and cardiorenal disease will only be discernible through longer-term trials on cardiovascular endpoints and cost-effectiveness.