European Journal of Medicinal Chemistry Reports最新文献

l-Arginine is an essential amino acid that plays a crucial role in various physiological processes. It serves as a precursor for nitric oxide (NO), which has potent antioxidant and anti-inflammatory properties. This review aims to comprehensively examine the medicinal importance of l-arginine as a natural antioxidant in preventing human health disorders. A comprehensive literature search was conducted using PubMed, Google Scholar, and other databases. Studies investigating the antioxidant effects of l-arginine and its potential role in preventing various diseases were included. l-Arginine has been shown to mediate NO production with strong antioxidant properties, scavenging free radicals and reducing oxidative stress. It has demonstrated therapeutic potential in preventing and mitigating various health conditions, including: Cardiovascular diseases, Neurodegenerative diseases, Metabolic disorders, Immune function and Anti-aging effects. l-Arginine is a potent natural antioxidant with significant medicinal importance. Its ability to scavenge free radicals, improve endothelial function, and support immune function makes it a promising therapeutic agent for preventing and treating a wide range of human health disorders. Further research is warranted to fully elucidate the mechanisms of action and optimal dosage for specific conditions.

Nanohybrid cerasomes represent a significant advancement in the field of drug delivery systems, offering a superior alternative to traditional cerasomes and liposomes. Cerasomes are biocompatible colloidal nanoparticles characterized by an additional polyorganosiloxane network layer that enhances their stability compared to conventional liposomes. The novel hybrid liposomal cerasome, featuring a partial ceramic or silica coating, has garnered substantial interest due to its unique structure. This structure provides better morphological stability than traditional liposomes and, in comparison to silica nanoparticles, significantly reduces overall stiffness and density. By incorporating liposomal architecture, cerasomes achieve greater biocompatibility than silica nanoparticles. This unique combination leverages the benefits of both liposomes and silica nanoparticles while mitigating their respective drawbacks, positioning cerasomes as an optimal drug delivery system. Nanohybrid cerasomes offer extended circulation residence time, enabling more efficient drug delivery to disease sites and facilitating the targeting of specific disease cells. Their potential as intracellular delivery vehicles for proteins, peptides, antisense compounds, ribozymes, and DNA is particularly noteworthy. The presence of a liposomal bilayer structure in cerasomes reduces rigidity and density, enhancing their stability and effectiveness as drug and gene delivery vehicles. This article reviews the techniques for preparing cerasomes and explores their applications in targeted drug and gene delivery systems, highlighting their advantages over conventional liposomes and silica nanoparticles.

A small library of arylsulfonamido-alkyl sulfamates was prepared by a two-step synthesis from readily available starting materials. The compounds were tested for their ability to inhibit bovine carbonic anhydrase II. Several of them were found as good competitive inhibitors holding K_i values as low as K_i = 0.9 μM (compound 47b). The activity was influenced by the substitution pattern of the arylsulfonamide moiety as well as the length of the spacer to the distal sulfamate group. Molecular docking studies were used to substantiate these findings. For the aryl-substituted analogues, the increase in inhibitory activity for compounds with a shorter spacer can be explained by stabilization via aromatic π-interactions. For the cyclopropyl or methylsulfonyl substituted analogues, their inhibitory activity can be attributed to their reduced steric hindrance. These results provide a basis for designing effective CA II inhibitors.

Ivermectin (IVR) is a 16-membered macrocyclic lactone of Nobel prize-honored distinction, showing a broad spectrum of biological activity, especially antiparasitic. We have recently designed a practical and scalable procedure for the synthesis of IVR derivatives with a rearranged oxahydrindene (hexahydrobenzofuran) ring that revealed improved antiparasitic activity compared to that of the native structure. Of note, the compounds that show activity towards parasites, very often are active against cancer cells and vice versa. However, the anticancer potential of IVR has not been studied intensively as yet, and there have been no reports on the effects of its synthetic derivatives against cancer cells. Thus, in the study reported, we thoroughly investigated the anticancer activity of IVR and its derivatives against a panel of four human cancer cell lines. We have identified a number of IVR derivatives with improved cytotoxicity and/or cancer cell-targeting selectivity compared to those of reference compounds. Cell cycle analysis has proved that selected compounds increased the number of cancer cells in the subG1 and G0/G1 phases (PC3, MDA-MB-231 and A549) or S/G2/M phase (HCT-116). The strong proapoptotic effect observed for the most promising IVR derivatives has been associated with a significant increase in caspase-3/7 activation and reactive oxygen species (ROS) production. Finally, these derivatives also showed significant inhibition of interleukin-6 (IL-6) cytokine secretion in cancer cells used. Our results indicate that chemical modification of IVR can lead to synthetic products with enhanced anticancer activity, which may provide an excellent starting point for further development of new IVR-derived agents for the treatment against cancer cells.

The outbreak of COVID-19 pandemic caused by the infection of SARS-CoV-2, has become a global crisis, threatening public health and disrupting global economy. Until now, effective therapeutics against COVID-19 and other coronavirus diseases are in high demand. Several antiviral strategies of drug discovery have identified many small molecules with potent anti-COVID-19 activity. Emetine, one of the main alkaloids of Carapichea ipecacuanha, has been found to exhibit potent antiviral activity against SARS-CoV-2, and other human coronaviruses, multiple RNA and DNA viruses at low nanomolar concentrations in different cell lines. In silico analysis reveals that emetine directly disrupts the activities of SARS-CoV-2 S-protein with host ACE2, and of RdRp-, 3CL-, PL-,and N- proteins. Moreover, emetine shows potent anti-inflammatory and anti-pulmonary arterial hypertensive properties by down-regulating the p38, ERK1/2, NF-κB and RhoA/Rho-kinase/CyPA/Bsg signaling pathways. At low doses, emetine is effective for treatment of COVID-19 patients and other viral infections in rodents. This review discusses the current findings on the antiviral efficacy of emetine against the emerging SARS-CoV-2 and other corona, RNA and DNA viruses, as well as its immunoregulatory pathways and clinical potential in COVID-19 infection for its development as antiviral prodrugs to treat current COVID-19 and future viral pandemics.

5-Fluorouracil (5FU) is a common chemotherapy drug for various cancers. It has exhibited large potentials for the treatment of both malignant and premalignant tumors. In the meantime, topical application of 5FU has been limited to surface pre-carcinogenic tumors. So far, a number of nano systems have been developed for encapsulation and targeted delivery of 5FU to improve its solubility, bioavailability, and functional characteristics, leading to the development of, for example, 5FU carriers in topical treatments. Due to their considerable advantages over ordinary therapies, nanotechnology-based drug delivery systems (DDSs), particularly polymeric nanocarriers (PNCs), have led to some sorts of evolution in many fields, including disease diagnosis and DDS. As a naturally occurring polymer, chitosan (CS) has long been regarded because of its biodegradability, biocompatibility, polycationic nature, non-toxicity, and non-allergenic nature. In addition, the pH-responsive nature of CS provides an exact drug dispersion in the cancer environment, converting it a promising carrier system. Utilization of 5-FU into carbon nanocarriers has indicated positive results such as targeted delivery to tumors and prevention of cancer activity. Researchers have successfully synthesized a handful of CS nanocarriers with distinctive characteristics for targeted delivery of 5FU; these come in different forms, including nano-sized particles (NPs), composites (NCs), emulsions (NEs), and fibers (NFs). This study reviews the mechanism of CS in different formulations by analyzing the physicochemical characteristics of the corresponding DDS in terms of morphology, surface charge, release profile, and encapsulation driving force. A more detailed analysis was performed on the most popular pharmaceutical applications of 5FU-loaded CS NPs. Effective facilitation of targeted delivery of 5FU and improvement of its therapeutic effects for various cancers by the CS were also indicated. Herein, the readers are introduced to nanoscale systems based on natural polymers like chitosan as promising platforms for cancer diagnosis and therapy. More recent discoveries on mechanistic anticancer behavior of 5FU-loaded CS NPs was further discussed.

Regardless of the area or the socio-economic status, cancer is currently the second or third prevalent cause of mortality ahead of stroke and coronary heart disease. Melphalan anticancer medication is the phenylalanine derivative of nitrogen mustard and has been demonstrated to successfully treat various types of cancers by suppressing the synthesis of deoxyribonucleic acid. Moreover, melphalan has been shown to exhibit synergetic effects in the treatment of multidrug-resistant tumors. However, its clinical application is restricted since it comes with severe adverse effects and significant drawbacks, such as non-target selectivity and short plasma half-life. To circumvent these constraints, various nanotechnological delivery platforms have been designed in recent years with the goal of improving melphalan delivery to tumor sites and regulating the EPR effect. This review article provides an overview of melphalan-based drug delivery systems (DDS), which include polymeric, lipid-based, and inorganic nanoformulations. The principal objective of this paper is to discuss the latest progress of the developed melphalan delivery systems and compare their essential factors such as particle size, size distribution, release profile, zeta potential, encapsulation and loading efficiency, and in vitro and in vivo assessments. Additionally, different platforms for the co-delivery of melphalan with other drugs have been reviewed, which provide promising future possibilities for cancer treatment. The information summarized in this context will contribute to developing a more practical approach for the future of cancer treatment.

NSAIDs, glucocorticoids, aminosalicylates, and immunosuppressants are nowadays the most commonly used anti-inflammatory medicines, although they have cosiderable side effects. Nanoparticles (NPs), notably metallic NPs, have gained appeal in the development of safer anti-inflammatory drugs. Because conventional NP synthesis methods are limited by environmentally unfriendly chemicals and high energy consumption, alternative green synthesis of metallic and metal oxide NPs, including plant-mediated synthesis, has piqued the interest of researchers due to phytochemicals that can reduce metal precursors and stabilize the generated NPs. This method is an eco-friendly, non-toxic, and cost-effective. This review aimed to highlight studies concerningthe anti-inflammatory activity of different plant-mediated green synthesis of metal and metal oxide nanoparticles with anti-inflammatory properties covering papers since 2017. According to the findings, the majority of the NPs tested were AgNPs. Noticeably, few investigations were conducted to assess the stability and safety of these NPs. Remarkably, someNPs exert more anti-inflammatory activity than plant extract itself and the standard. Some anti-inflammatory tests were limited to in vitro testing. Obviously, there is a lack of information regarding the safety issues of these NPs and the determination of their active doses. Thus, further invitro and invivo pharmacological and toxicological studiesare required for these metal and metal oxide NPs to identify medicinal uses and avoid unintended adverse consequences. It is also urgent to test the stability of these NPs in various dosage forms after determining the optimal active dose.

Galectin-1 (gal-1) emerges as a potential biomarker for cancer diagnosis, prognosis, and therapy. Gal-1 plays a pivotal role in multiple stages of tumor progression, encompassing tumor transformation, tumor cell adhesion and migration, angiogenesis, and evasion of immune responses. Despite efforts to develop carbohydrate-based gal-1 inhibitors targeting the carbohydrate recognition domain, challenges still persist such as limited selectivity due to high water solubility, poor pharmacokinetics, and expensive synthetic routes that limit their effectiveness against overexpressed gal-1 in cancer cells. Therefore, next generation anticancer agents targeting gal-1 with improved pharmacokinetics and target selectivity may overcome current challenges. Various synthetic strategies have been explored, including substituting the carbohydrate nucleus with bioactive heterocycles in small molecules, employing sugar mimetics, or investigating alternative allosteric inhibition with peptides and peptidomimetics. This review describes gal-1 multifaceted roles in tumor biology, rationalized approaches, design strategies for non-carbohydrate gal-1 inhibitors, and provides insights into structure-activity relationship and gal-1 inhibitory mechanisms.

Trans-ferulic acid, is one of the many biologically significant bioactive components of Datura. It has wide range of potential applications in the food industry, health, and cosmetics industries. Trans-ferulic acid possess myriad properties like anti-inflammatory, anti-aging, antiangiogenic, anticancer, antimicrobial, and antioxidant properties. To exploit its antioxidant and anti-inflammatory properties, first of all, trans-ferulic acid loaded tragacanth/chitosan nanoparticles (TFA loaded TGCA-NPs) were synthesized by ionic gelation method using tragacanth and chitosan as polymers. Tragacanth used to encapsulate the trans-ferulic acid is a polysaccharide gum, which is used all over the world in industries ranging from the food industry to healthcare systems due to its availability, affordability, non-toxicity, and environmental friendliness. The synthesized nanoparticles were then characterized by using techniques like FTIR, UV–Vis Spectroscopy, SEM and TEM. The particle size of nanoparticles thus obtained ranged from 105 nm to 250 nm. SEM micrograph of nanoparticles showed tiny rod-like structures, which appear to be coated on the polymer. TEM images showed somewhat sphere-shaped nanoparticles with a projecting rod-like structure that might be due to the trans-ferulic acid encapsulation in tragacanth-chitosan polymer. Decent antimicrobial activity of synthesized nanoparticles was observed against pathogenic bacteria named Staphylococcus aureus. Hemocompatibility of trans-ferulic acid loaded tragacanth-chitosan nanoparticles was also examined. The antioxidant activity was evaluated by DPPH radical scavenging assay, in which synthesized nanoparticles showed 41.62 % radical scavenging activity. For in-vitro anti-inflammatory activity Human Red Blood Cell membrane stabilization method (HRBC method) was used, and the results showed higher protection by the synthesized nanoparticles in comparison to the pure trans-ferulic acid and blank nanoparticles.