Current topics in medicinal chemistry最新文献

Cardiovascular disorders develop the highest rates of mortality and morbidity worldwide, emphasizing the need for novel pharmacotherapies. The Chinese medicinal plant S. baicalensis has a number of major active components, one of which is called baicalin. According to emerging research, baicalin reduces chronic inflammation, immunological imbalance, lipid metabolism, apoptosis, and oxidative stress. Baicalin improves endothelial function and protects the cardiovascular system from oxidative stress-induced cell injury by scavenging free radicals and inhibiting xanthine oxidase. Therefore, it helps prevent CVD such as hypertension, atherosclerosis, and cardiac arrest. In this review, the therapeutic effects of baicalein are discussed in relation to both the prevention and management of cardiovascular diseases.

Non-fused pyrimidine scaffold is a significant component for designing new drugs. The review emphasizes the pharmacological importance of non-fused pyrimidine-containing moieties based on the broad spectrum of activities such as antiprotozoal, antibacterial, antimycobacterial, anticancer, anti-inflammatory activity, and CNS depressant. Pyrimidine derivatives are fascinating entities that display biological activities for the treatment of cancer. It also highlights the tendency of non-fused pyrimidine derivatives to suppress cell growth by obstructing the activity of VCP, CDK-2, EGFR, ATR, EphB4 & EphA2, PDGF as well as inhibitory action towards different cell lines such as MCF-7, HeLa, NCI/ADR-RES, NCIH23, HOP-92, HCT-116, OV-3, MOLT-4, PC-3, MDA-MB-231, MALME-3M, K562 and Bcr-Abl. The review details the importance of morpholine, piperidine, and pyrrolidine ring substitutions on pyrimidine moiety as well as the role of H-bonding and amino linkage along with antibacterial activity due to the presence of pleuromutilin and tetrazole molecules. Researchers were motivated to develop and enhance the non-fused pyrimidine scaffold to uncover novel medicines by reading this review article.

Healthy skin is essential for balanced health. Currently, skin diseases are considered a major global health issue, impacting individuals of all ages. Skin conditions can vary broadly, ranging from common issues like acne and eczema to more serious diseases such as psoriasis, melanoma, and other types of skin cancer. In recent years, computational methods have appeared as powerful tools for explaining the lurking mechanisms of skin diseases and the advancement of the discovery regarding updated therapeutics. This review spotlights the notable researches that have been performed in using computational approaches such as virtual screening, molecular modelling, and molecular dynamics simulations to discover potential treatments for dermatological conditions such as eczema, psoriasis, acne vulgaris, skin cancer, and tyrosinase-related disorders. Moreover, using in silico methods, researchers have explored the molecular interactions between cosmetic actives and skin targets, providing insights into the binding affinities, stability, and efficacy of these compounds. This computational exploration allows the identification of potential off-target effects and toxicity profiles, ensuring that only the most promising candidates proceed to clinical testing. In addition, the use of molecular dynamics simulations helps to understand conformational changes and interaction dynamics over time, further refining the selection of effective cosmetic actives. Overall, the integration of computational chemistry into dermo-cosmetic research has immense potential to accelerate the discovery and development of innovative treatments to improve skin health and address dermatological concerns.

Introduction: Hyperpigmentation disorders are caused by excess production of the pigment melanin, catalyzed by the enzyme tyrosinase. Novel tyrosinase inhibitors are needed as therapeutic agents to treat these conditions.

Method: To discover new inhibitors, we performed a virtual screening of the ZINC20 library containing 1.4 billion compounds. An initial filter for drug-likeness, ADMET properties, and synthetic accessibility reduced the library to 10,217 hits. Quantitative structure-activity relationship (QSAR) modeling of this subset predicted nanomolar inhibitory potency for several chemical scaffolds. Comparative molecular docking studies and rigorous binding energy calculations further prioritized four cysteine-containing dipeptide compounds based on predicted strong binding affinity and mode to tyrosinase.

Results: Microsecond-long molecular dynamics simulations provided additional atomistic insights into the stability of inhibitor-enzyme binding interactions. This integrated computational workflow effectively sampled an extremely large chemical space to discover four novel tyrosinase inhibitors with half-maximal inhibitory concentration values below 10 nM.

Conclusion: Overall, this demonstrates the power of virtual screening and multi-faceted computational techniques to accelerate the discovery of potent bioactive ligands from massive compound libraries by efficiently sampling chemical space.

Introduction: The mutual activations of multiple signaling pathways are the key factors in the development and progression of myocardial cell injuries.

Objective: This research aimed to compare the different degrees of myocardial injury after coronary stenting, permanent pacemaker implantations, or cardiac radiofrequency ablation and to investigate the effects of the mutual activation of TNF-α/NF-κB, TLR2/TLR4, and ROS/MDA signaling pathways on myocardial injury in elderly patients after coronary stents or permanent pacemakers or radiofrequency ablation.

Methods: We determined reactive oxygen species (ROS), malondialdehyde (MDA), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor- α (TNF-α) and high-sensitive cardiac troponin T (hs-cTnT) as a marker of myocardial injury in patients.

Results: The levels of ROS, MDA, TLR2, TLR4, NF-κB, TNF-α, and hs-cTnT were increased in patients with permanent pacemaker implantations when compared to patients with cardiac radiofrequency ablation (P < 0.01) at 6 months and were further increased in patients with coronary stenting compared to patients with cardiac radiofrequency ablation and permanent pacemaker implantations at 6 months, respectively (P < 0.01). This research confirmed that ROS, MDA, TLR2, TLR4, NF-κB, and TNF-α predicted myocardial injury severity.

Conclusion: Oxidative stress (ROS/MDA signaling pathway) may be linked to immune response (TLR2/TLR4 signaling pathway) and pro-inflammatory response (TNF-α/NF-κB signaling pathway) in myocardial injury, and ROS/MDA signaling may play a dominant role.

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.