Current Medicinal Chemistry - Volume 31, Issue 27, 2024

Background: Iron deficiency and iron-related disorders are common health issues worldwide, affecting a significant proportion of the population. Diagnosis and management of these disorders rely heavily on using various iron-related biomarkers that can provide valuable clinical information. Objective: This review article provides an overview of the most commonly used iron-related biomarkers, including serum ferritin, transferrin saturation, soluble transferrin receptor, zinc protoporphyrin, and free erythrocyte protoporphyrin. Other emerging biomarkers, such as hepcidin and retinol-binding protein 4, are also discussed. Results: Iron plays a vital role in various physiological processes, including oxygen transport, energy metabolism, and DNA synthesis. The article highlights the advantages and limitations of iron biomarkers and their clinical applications in diagnosing and managing iron deficiency and iron-related anemia. Conclusion: Using iron-related biomarkers in screening and monitoring programs can improve patient outcomes and reduce healthcare costs.

Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no definitive treatment, which requires ongoing research into its etiology. Additionally, the association between prostatitis and an elevated risk of prostate cancer highlights the importance of comprehending androgen involvement in prostatitis. This paper examines the current understanding of androgen signaling in prostatitis and explores contemporary therapeutic approaches. It was reviewed Medline articles comprehensively, using keywords such as nonbacterial prostatitis, prostatitis infertility, androgen role in prostatitis, and chronic pelvic pain. Several cellular targets are linked to androgen signaling. Notably, the major tyrosine phosphatase activity (cPAcP) in normal human prostate is influenced by androgen signaling, and its serum levels inversely correlate with prostate cancer progression. Androgens also regulate membrane-associated zinc and pyruvate transporters transduction in prostate cells, suggesting promising avenues for novel drug development aimed at inhibiting these molecules to reduce cancer tumor growth. Various therapies for prostatitis have been evaluated, including antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha-blockers, 5α-reductase inhibitors, and androgen receptor antagonists. These therapies have demonstrated varying degrees of success in ameliorating symptoms.In conclusion, aging decreases circulating T and intraprostatic DHT, altering the proper functioning of the prostate, reducing the ability of androgens to maintain normal Zn²⁺ levels, and diminishing the secretion of citrate, PAcP, and other proteins into the prostatic fluid. The Zn²⁺-transporter decreases or is absent in prostate cancer, so the pyruvate transporter activates. Consequently, the cell ATP increases, inducing tumor growth.

Brucellosis remains one of the major zoonotic diseases worldwide. As a causative agent of brucellosis, it has many ways to evade recognition by the immune system, allowing it to replicate and multiply in the host, causing significant harm to both humans and animals. The pathogenic mechanism of Brucella has not been elucidated, making the identification of drug targets from the pathogenic mechanism a challenge. Metalloenzymatic targets and some protein targets unique to Brucella are exploitable in the development of inhibitors against this disease. The development of specific small molecule inhibitors is urgently needed for brucellosis treatment due to the antibiotic resistance of Brucella. This review summarizes the research on small molecule inhibitors of Brucella, which could be instructive for subsequent studies.

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/ intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti- bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Atherosclerosis remains a leading contributor to cardiovascular disease-associated morbidity and mortality. Interestingly, atherosclerosis-associated mortality rate is higher in men than women. This suggested a protective role for estrogen in the cardiovasculature. These effects of estrogen were initially thought to be mediated by the classic estrogen receptors, ER alpha, and beta. However, genetic knockdown of these receptors did not abolish estrogen’s vasculoprotective effects suggesting that the other membranous Gprotein coupled estrogen receptor, GPER1, maybe the actual mediator. Indeed, in addition to its role in vasotone regulation, this GPER1 appears to play important roles in regulating vascular smooth cell phenotype, a critical player in the onset of atherosclerosis. Moreover, GPER1-selective agonists appear to reduce LDL levels by promoting the expression of LDL receptors as well as potentiating LDL re-uptake in liver cells. Further evidence also show that GPER1 can downregulate Proprotein Convertase Subtilisin/ Kexin type 9, leading to suppression of LDL receptor breakdown. Here, we review how selective activation of GPER1 might prevent or suppress atherosclerosis, with less side effects than those of the non-selective estrogen.

Nanoparticles have been crucial in redesigning tumour eradication techniques, and recent advances in cancer research have accelerated the creation and integration of multifunctional nanostructures. In the fight against treatment resistance, which has reduced the effectiveness of traditional radiation and chemotherapy, this paradigm change is of utmost importance. Graphene oxide (GO) is one of several nanoparticles made of carbon that has made a splash in the medical field. It offers potential new ways to treat cancer thanks to its nanostructures, which can precisely transfer genetic elements and therapeutic chemicals to tumour areas. Encapsulating genes, protecting them from degradation, and promoting effective genetic uptake by cancer cells are two of GO nanostructures' greatest strengths, in addition to improving drug pharmacokinetics and bioavailability by concentrating therapeutic compounds at particular tumour regions. In addition, photodynamic treatment (PDT) and photothermal therapy (PTT), which use GO nanoparticles to reduce carcinogenesis, have greatly slowed tumour growth due to GO's phototherapy capabilities. In addition to their potential medical uses, GO nanoparticles are attractive vaccine candidates due to their ability to stimulate cellular and innate immunity. These nanoparticles can be used to detect, diagnose, and eradicate cancer because they respond to certain stimuli. The numerous advantages of GO nanoparticles for tumour eradication are attributed in large part to their primary route of internalisation through endocytosis, which guarantees accurate delivery to target locations. The revolutionary potential of multifunctional nanostructures in cancer treatment is highlighted in this extensive compendium that examines current oncological breakthroughs.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Multiple myeloma is a plasma cell neoplasm. The emergence of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has improved the prognosis of multiple myeloma patients. However, some patients are still insensitive to conventional therapy or frequently relapse after remission. Chemotherapy based on proteasome inhibitors or immunomodulatory drugs is ineffective in controlling the progression of relapsed refractory multiple myeloma. No consensus has been reached on treating relapsed refractory multiple myeloma to date. Recently chimeric antigen receptor T cells therapy has shown promising results that could achieve rapid remissions of patients and improve their prognoses. Additionally, most patients in chimeric antigen receptor T cell clinical trials were triple-refractory multiple myeloma patients, indicating that chimeric antigen receptor T cell immunotherapy could overcome drug resistance to new drugs. Since single immunotherapies are prone to acquired resistance, combination immunotherapies based on emerging immunotherapies may solve this issue. Achieving complete remission and minimal residual disease negative status as soon as possible is beneficial to patients. This paper reviewed the main chimeric antigen receptor T cell products in relapsed refractory multiple myeloma, and it explained the drug resistance mechanism and improvement methods of chimeric antigen receptor T cells therapy. This review summarized the best beneficiaries of chimeric antigen receptor T cell therapy and the salvage treatment of disease recurrence after chimeric antigen receptor T cell therapy, providing some ideas for the clinical application of chimeric antigen receptor T cells.

Background: Iron chelators (ICs) have recently emerged as one of the new methods of treatment for viral infections. This study aimed to evaluate the efficiency and safety of natural ICs compared to synthetic ICs. Natural and synthetic ICs are the most common therapeutic agents tested for the treatment of viral infections. When evaluated against synthetic ICs, natural ICs are probably favored owing to their lower toxicity and safer properties. The main objective of the present systematic review was to assess the current evidence on the role of pharmacological mechanisms in the treatment of viral infections. Methods: This study was designed as a systematic review in which search strategies were focused on two electronic databases, PubMed, and Scopus, between 2017 and 2021. A search filter with two subjects, “iron chelators” and “viral infection”, was employed. Results: According to the results, both natural and synthetic chelators had a considerable impact on the treatment of viral infections via various mechanisms, with natural ICs being the most extensively used. Conclusion: Natural and synthetic ICs exert their effects through different pharmacological mechanisms. Among these compounds, natural chelators are more widely used due to their safety, efficacy, and a wider range of applications.

Background: Osteoarthritis (OA) represents a persistent degenerative joint ailment. As OA advances, profound joint pain coupled with diminished joint function inflicts substantial physical distress and psychological strain on patients. Presently, pharmacological solutions for arthritis remain limited, primarily encompassing analgesics and joint replacement surgical procedures. Hence, non-operative strategies to mitigate osteoarthritis progression have captured significant attention in orthopedic research. Objective: This study aims to discern a definitive causal linkage between ADAMTS-4/5 and osteoarthritis through Mendelian randomization analysis. Moreover, it seeks to anticipate the therapeutic efficacy of a suite of emergent hydroxyquinolines for osteoarthritis using the Quantitative Structure-Activity Relationship (QSAR) methodology. Methods: Within this study, genetic variants specific to knee osteoarthritis were procured as exposure variables from a genome-wide association study (GWAS). Genetic variant data for ADAMTS-4/5 served as the endpoint to evaluate the causal nexus employing univariate Mendelian randomization. This analysis underpins the hypothesis that ADAMTS-4/5 presents a promising therapeutic target for osteoarthritis management. The suppressive properties of novel hydroxyquinolines against ADAMTS-4/5 were subsequently examined through conformational analyses, underscoring the potential of these compounds as therapeutic candidates for osteoarthritis. Results: IVW outcomes from the Mendelian randomization revealed a significant association of KOA (OR: 1.1675, 95% CI: 1.0003-1.3627, P = 0.0495) with ADAMTS-5. However, KOA (OR: 1.0801, 95% CI: 0.9256-1.2604, P = 0.3278) displayed no evident connection with ADAMTS-4. Notably, the instrumental variables manifested neither heterogeneity nor horizontal pleiotropy. In this research endeavor, 16 pharmacological models were formulated via the CoMSIA method within 3D conformational relationship evaluations. A synergistic interplay of hydrophobic, spatial, and hydrogen-bonded receptor domains emerged as the most predictively potent. The cross-validation coefficient q2 for the optimum model stood at 0.716, with a principal component score of 5, a regression coefficient r2 of 0.971, a standard estimation error of 0.351, and an f-value of 156.951. Such metrics intimate the commendable predictive prowess of our devised CoMSIA models. Conclusion: The research unearthed a robust causal interrelation between ADAMTS-5 and osteoarthritis via Mendelian randomization. Furthermore, a credible drug model targeting ADAMTS-5 was constructed. Collectively, these findings illuminate a path forward in the pursuit of target-specific drugs for osteoarthritis management in subsequent investigations.