Abstract Cardiovascular diseases (CVDs), including atherosclerosis, congestive heart failure, and hypertension, are most commonly observed in middle-aged and elderly individuals. Approximately 15 million people die from them every year worldwide. CVDs are associated with high morbidity, disability, and mortality rates, posing a significant threat to public health. Although the importance of natural medicines in treating CVDs has become increasingly prominent, there is still much to be discovered about their composition and mechanisms of action. With the rise of network pharmacology as a valuable tool to understand how natural medicines work, researchers can study the body's responses to disease stimuli and drug therapy by constructing a “component–target–pathway–disease” interaction network. In this work, we summarized the application of network pharmacology in the study of CVDs. We also discussed the challenges and opportunities by this tools, hoping to provide suggestions for the treatment of the disease in the future.

Since their first synthesis by Atkinson in 1952, gem-difluorocyclopropanes (gem-DFCPs) have become indispensable building blocks in both organic synthesis and medicinal chemistry. These fluorinated three-membered carbocycles exhibit remarkable reactivity patterns due to their inherent ring strain and the electronic effects of fluorine substitution, which facilitate diverse ring-editing transformations. This comprehensive review systematically examines recent advancements in gem-DFCPs-mediated ring restructuring reactions, including their transformation into four-, five-, six-, and extended-membered ring systems. Particular emphasis is placed on elucidating the underlying reaction mechanisms, stereochemical control elements, and practical synthetic applications. Through this analysis, we aim to provide a structured framework that guides future research in the rapidly expanding field of fluorinated cycloaddition chemistry.

Abstract Proteolysis-targeting chimeras (PROTACs) are driving medicinal chemistry progress, yet efficient synthesis and rational linker design remain two critical bottlenecks for their clinical translation. Those core challenges directly limit the advancement of PROTACs from preclinical research to practical application. This review focuses on state-of-the-art enabling chemical strategies to address these key bottlenecks, ensuring tight relevance to PROTACs development needs. The modular assembly can be streamlined by click chemistry, multicomponent, and late-stage C–H functionalizations, whereas microscale and solid-phase platforms can be used to deliver thousands of analogues in days without purification. In this work, we emphasize covalent sulfonyl fluoride warheads and photocaged or photoswitchable scaffolds that provide spatiotemporal control of degradation. The employment of dynamic combinatorial chemistry, DNA-encoded libraries, and intracellular self-assembly further expands chemical space and accelerates hit triage. At last, we outline how artificial intelligence-driven modeling integrates these data to predict linker length, exit vector geometry, and ADME profiles, shortening iterative design cycles. Collectively, these chemistry-centric innovations are turning PROTACs from a conceptual breakthrough into a practical drug-discovery engine by directly addressing the synthesis, optimization, and functional control challenges that have impeded their clinical advancement.

This paper aims to improve the synthetic process of molnupiravir based on previously reported synthetic routes. The route begins with uracil (ML-2), which is protected with an isopropyl group to yield ML-3 (Step 1), followed by an esterification and a triazolation reaction (Steps 2 and 3) to produce ML-5, which, via a hydroxylation reaction and deprotection (Steps 4 and 5), gives the target product ML-1. Nuclear magnetic resonance (1H NMR) and mass spectra were used for chemical structure identification. There are mainly the following improvements, including: (1) replacing the separate addition of acetone and concentrated H2SO4 with 2,2-dimethoxypropane and catalytic p-toluenesulfonic acid monohydrate in Step 1, simplifying the workup operation and reducing the dosage of reaction solvent. (2) Optimize the synthesis conditions of ML-5, reduce the formation of impurities, and improve the purity of the crude product from 43.12 to 85.21%. (3) Three impurities were isolated, two of which are new compounds. This article lays a foundation to obtain molnupiravir with controllable quality and a stable process for the treatment of coronavirus disease 2019.

Targeting cyclin-dependent kinase (CDK) families is a promising strategy for cancer therapy due to the close association between CDKs and an abnormal cell cycle or transcriptional regulation. However, after extensive clinical use, small molecule inhibitors of CDKs have also exposed issues, such as off-target effects or acquired drug resistance. Targeting protein degradation technology, which has been validated to be effective for many targets, has undergone more than 20 years of development, and some of these methods have been pushed into clinical trials. In this review, we summarized some successful reports on CDK-targeted degradation during recent years. Moreover, some challenging issues and future development trends are highlighted in the prospect section, which might provide updated insight into the development of novel CDK-targeted degraders with great potential as a new weapon for cancer therapy.

Abstract While some Coleus species have demonstrated anti-HIV activity, the potential of Mayana (Coleus scutellarioides Benth.) remains largely unexplored. This study therefore aimed to investigate the anti-HIV potential of phytoconstituents from Mayana using in silico methods. Phytochemicals from Mayana were identified using gas chromatography–mass spectrometry and their binding affinity against HIV-1 integrase (IN), protease (PR), and reverse transcriptase (RT) were evaluated through molecular docking simulations. In this work, a total of 32 individual compounds were identified. Stigmasterol was found to have the highest binding affinity to HIV IN (−8.571 kcal/mol) and HIV PR (−10.250 kcal/mol), whereas caryophyllene showed the highest affinity to HIV RT (−9.625 kcal/mol). These compounds also demonstrated multitarget interactions, suggesting potential inhibitory effects. However, compared with synthetic drugs such as amprenavir (−9.421 kcal/mol for PR), raltegravir (−9.825 kcal/mol for IN), and nevirapine (−9.748 kcal/mol for RT), the phytoconstituents had lower binding affinities. Pharmacokinetic predictions revealed that the top-ranked phytochemicals conform to Lipinski's Rule of Five, indicating favorable drug-like properties. Overall, Mayana contains bioactive phytoconstituents with promising affinity for key HIV-1 enzymes, supporting the potential of Mayana as a source of novel anti-HIV leads. However, further in vitro and in vivo studies are needed to confirm the efficacy, safety, and pharmacokinetic profile.

Abstract Drug delivery often faces challenges from biological barriers, including the skin and mucosa. Penetration enhancers (PEs) are commonly employed to improve the delivery of poorly permeable drugs. Among them, volatile oils derived from natural plants have emerged as promising candidates due to their rapid action, minimal side effects, and high efficiency. This paper provides a brief introduction to biological barriers and highlights the potential of volatile oils as PEs and their underlying mechanisms. Their role in improving transdermal and transmucosal drug delivery has been explored by a comprehensive review of recent research, which provides valuable insights into their future application in pharmaceutical formulations.

Pravastatin sodium (PS) is a hydrophilic statin lipid-lowering drug that reduces low-density lipoprotein levels in the blood by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. It is known to exist in 17 crystalline forms, with some different crystalline forms overlapping in the powder diffraction patterns, making it difficult to control the purity of the crystalline forms. In this study, we aimed to determine the purity of PS crystals using powder X-ray diffraction (PXRD), mid-infrared (MIR) spectroscopy, and Raman techniques. The predictive ability of the partial least squares (PLS) model was constructed and assessed using SPXY, K_S, and Random methods at different partitioning ratios. PLS calibration curves were established based on the relationship between PXRD, MIR, and Raman data and the content of a solid forms of PS (PS-A) in different ranges (full and partial spectra) using different preprocessing algorithms such as multiplicative scattering correction, standard normal variable, Savitzky–Golay filtering, and derivative spectroscopy, or a combination of them. The results showed that the calibration model (y = 0.999x + 0.008 with R 2 = 0.999) established using the PXRD method was better, with a low detection limit (1.52%) and quantification limit (4.60%). In addition, by analyzing the testing results of the blind sample, it was found that the confidence intervals of the predicted values of MIR and Raman were wider, indicating a large uncertainty of their parameter estimation. Therefore, it will be better to select the calibration model established by the PXRD method to determine the purity of PS in actual production. This can provide more reliable methodological support for the quality control of pharmaceutical products.