Current topics in medicinal chemistry最新文献

Aims: The aim of the current study was to explore the anti-diabetic potential of Ochradenus aucheri Boiss (O. aucheri).

Method: All the fractions of O. aucheri were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor.

Results: The preliminary screening showed that all the fractions including n-hexane (38.0 ± 1.38 μg/mL), dichloromethane (92.6 ± 6.18 μg/mL), ethyl acetate (29.2 ± 0.51 μg/mL) and n-butanol (361.8 ± 5.80 μg/mL) displayed significant α-glucosidase inhibitory activity. The activity-directed fractionation and purification of ethyl acetate fraction led to the isolation of one new sesquiterpenoid, Jardenol (1), and two known metabolites: β-stitosterol-3-O-β-D-glucopyranoside (2) and β-Sitosterol (3). To the best of our knowledge, these metabolites have not been isolated from this plant previously. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. Compound 1 showed significant α-glucosidase inhibition with an IC50 value of 138.2 ± 2.43 μg/mL as compared to positive control acarbose (IC50 = 942.0 ± 0.60 μg/mL). Additionally, in-silico docking was employed to predict the binding mechanism of compound 1 in the active site of the target enzyme, α-glucosidase. The docking results suggested that the compound forms strong interactions at the catalytic site of α-glucosidase.

Conclusion: The results of the present study indicated that the newly purified secondary metabolite, Jardenol, can be a promising anti-diabetic compound.

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Research shows that the development of AD is linked to neuroinflammation, endoplasmic reticulum stress, mitochondrial dysfunction, cell death, and abnormal cholinergic signaling. Glycyrrhiza compounds contain active ingredients and extracts that offer multiple benefits, including targeting various pathways, high efficacy with low toxicity, and long-lasting therapeutic effects. These benefits highlight the significant potential of Glycyrrhiza compounds for preventing and treating AD. This review summarizes recent advancements in Glycyrrhiza compounds for preventing and treating AD. It focuses on their inhibitory effects on key signaling pathways, such as Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and cholinergic signaling. This study aims to establish a scientific framework for using Glycyrrhiza compounds in the clinical prevention and treatment of AD and to support the development of new therapeutic interventions.

Anacardic acids are natural compounds found in various plant families, such as Anacardiaceae, Geraniaceae, Ginkgoaceae, and Myristicaceae, among others. Several activities have been reported regarding these compounds, including antibacterial, antioxidant, anticancer, anti-inflammatory, and antiviral activities, showing the potential therapeutic applicability of these compounds. From a chemical point of view, they are structurally made up of salicylic acids substituted by an alkyl chain containing unsaturated bonds, which can vary in number and position, determining their bioactivity and differentiating them from the various existing forms. Our work aimed to explore the potential of anacardic acids, based on studies that address the bioactivity of these compounds, as well as to establish a greater understanding of the structure-activity relationship of these compounds through in silico methods, with a focus on the elucidation of a possible drug target through the application of computer-aided drug design, CADD.

Introduction: Iron oxide nanoparticles demonstrate tremendous potential in preserving the ecological balance of the environment since they act as antimicrobial agents and efficient photocatalysts. However, environmental sustainability has challenged the synthesis protocols of nanomaterials.

Method: This study compares the green synthesis method with the scalable chemical synthesis method. In this work, Iron oxide nanoparticles were fabricated via the green chemistry technique utilizing the leaf extract of Mentha spicata (M-IONP) and also via the chemical co-precipitation method (C-IONP). The synthesized IONPs were analyzed by different characterization methods such as XRD, FTIR, SEM analysis, ZETA potential measurements, and DLS spectroscopy analysis.

Results: The biosynthesized and chemically synthesized IONPs were analyzed for their mechanistic action against different applications like antimicrobial, antioxidant, and degradation of harmful dyes. Interestingly, the biosynthesized IONPs (M-IONP) exhibited more effective antimicrobial efficacy towards Gram-positive and Gram-negative organisms than chemically synthesized IONPs.

Conclusion: The green synthesized M-IONP also showed significant antioxidant propensity similar to that of the standards taken. Additionally, green-synthesized M-IONP exhibited enhanced degradation efficacies against Methylene blue, chromium, and sulphamethoxazole in comparison to chemically synthesized IONP.

Over the past few years, photocatalytic methods have shown great promise as low-cost, environmentally friendly, and sustainable technologies. During the development of photochemistry, a variety of sources of light were used, including sunlight, compact fluorescent lamps, lasers, and even light-emitting diodes. As a part of preparing diverse organic compounds, the photochemical approach was used, for instance, to form rings, arylated compounds, cycloaddition, functionalized compounds, dehalogenated compounds, oxidized compounds, reduced compounds, isomers, and sensitized compounds. Solar energy is a renewable resource that can be harvested from the sun and this light energy can be changed into chemical energy with the help of photocatalysts. During this green approach, electron-hole pairs are generated in photocatalysts in order to begin reactions by using solar light. It has been highlighted in this article that there have been impressive developments in the use of light, mainly the solar light, to promote important organic reactions, which would otherwise be unattainable under thermal conditions.

Introduction: Oral squamous cell carcinoma (OSCC) is a prevalent malignant condition. This study aimed to investigate the role of mTORC1 signaling and develop a prognostic model for OSCC.

Materials and methods: The single-sample gene set enrichment analysis (ssGSEA) algorithm was utilized to calculate the Z-Score of Hallmarks in OSCC, followed by univariate Cox regression analysis to identify processes associated with prognosis. Weighted gene co-expression network analysis (WGCNA) was performed using transcriptomic data from the cancer genome atlas (TCGA) cohort to identify genes correlated with mTORC1 signaling. A six-gene prognostic model was constructed using multifactorial Cox regression analysis and validated using an external dataset.

Results: The study uncovered a strong linkage between mTORC1, glycolysis, hypoxia, and the prognosis of OSCC. mTORC1 signaling emerged as the most significant risk factor, negatively impacting patient survival. Additionally, a six-gene prognostic risk score model was developed which provided a quantitative measure of patients' survival probabilities. Interestingly, within the context of these findings, TP53 gene mutations were predominantly observed in the high-risk group, potentially underlining the genetic complexity of this patient subgroup. Additionally, differential immune cell infiltration and an integrated nomogram were also reported.

Conclusion: This study highlights the importance of mTORC1 signaling in OSCC prognosis and presents a robust prognostic model for predicting patient outcomes.

Introduction: Single nucleotide polymorphisms (SNPs) are pivotal in clinical genetics, serving to link genotypes with disease susceptibility and response to environmental factors, including pharmacogenetics. They also play a crucial role in population genetics for mapping the human genome and localizing genes. Despite their utility, challenges arise when molecular genetic studies yield insufficient or uninformative data, particularly for socially significant diseases. This study aims to address these gaps by proposing a method to predict allelic variants of SNPs.

Method: Using quantitative PCR and analyzing body composition data from 150 patients with their voluntary informed consent, we employed IBM SPSS Statistics 29.0 for data analysis. Our prototype formula, exemplified by allelic variant ADRB2 (rs1042713) = 0.257 + 0.639 * allelic variant ADRB2 (rs1042714) - 0.314 * allelic variant ADRB3 (rs4994) + 0.191 * allelic variant PPARA (rs4253778) - 0.218 * allelic variant PPARD (rs2016520) + 0.027 * body weight + 0.00001 * body weight², demonstrates the feasibility of predicting SNP allelic variants.

Results: This method holds promise for diverse diseases, including those of significant social impact, due to its potential to streamline and economize molecular genetic research. Its ability to stratify disease risk in the absence of complete SNP data makes it particularly compelling for clinical and laboratory geneticists.

Conclusion: However, its translation into clinical practice necessitates the establishment of a comprehensive SNP database, especially for frequently analyzed SNPs within the implementing institution.

N-heterocycles represent a predominant and unique class of organic chemistry. They have received a lot of attention due to their important chemical, biomedical, and industrial uses. Food and Drug Administration (FDA) approved about 75% of drugs containing N-based heterocycles, which are currently available in the market. N-Heterocyclic compounds exist as the backbone of numerous natural products and act as crucial intermediates for the construction of pharmaceuticals, veterinary items, and agrochemicals frequently. Among N-based heterocyclic compounds, bioactive N,N-heterocycles constitute a broad spectrum of applications in modern drug discovery and development processes. Cefozopran (antibiotic), omeprazole (antiulcer), enviradine (antiviral), liarozole (anticancer), etc., are important drugs containing N,N-heterocycles. The synthesis of N,Nheterocyclic compounds under sustainable conditions is one of the most active fields because of their significant physiological and biological properties as well as synthetic utility. Current research is demanding the development of greener, cheaper, and milder protocols for the synthesis of N,N-heterocyclic compounds to save mother nature by avoiding toxic metal catalysts, extensive application of energy, and the excessive use of hazardous materials. Nanocatalysts play a profound role in sustainable synthesis because of their larger surface area, tiny size, and minimum energy; they are eco-friendly and safe, and they provide higher yields with selectivity in comparison to conventional catalysts. It is increasingly demanding research to design and synthesize novel bioactive compounds that may help to combat cancer since the major causes of death worldwide are due to cancer. Hence, the important uses of nanocatalysts for the one-pot synthesis of biologically potent N,N-heterocycles with anticancer activities have been presented in this review.