Current Topics in Medicinal Chemistry - Online First

To investigate the antimicrobial potential of methanol fruit extract of Solanum xanthocarpum against Methicillin-Resistant Staphylococcus aureus (MRSA) and elucidate its mode of action.

The rise of antimicrobial resistance (AMR) demands the exploration of alternative therapeutic strategies to combat resistant pathogens.

To evaluate the efficacy of Solanum xanthocarpum methanol extract against MRSA, and identify its active constituents and mechanism of action.

The fruits of Solanum xanthocarpum were extracted using various solvents, with hexane and methanol yielding the highest results. Microbroth dilution assays assessed antimicrobial activity, while in vitro assays such as Alamar blue, Scanning Electron Microscopy (SEM), protein, and nucleic acid leakage examined metabolic disruption and cell membrane integrity. Gas Chromatography-Mass Spectrometry (GC-MS) was used to identify active compounds, and molecular docking studies assessed interactions with key MRSA proteins.

The methanol extract demonstrated significant antimicrobial activity against MRSA, causing metabolic disruption and leakage of cellular contents as evidenced by various in vitro assays including alarm blue, SEM, and protein and nucleic acid leakage assay. GC-MS analysis identified alpha-linoleic acid and palmitic acid as key active components. Molecular docking studies confirmed their inhibition of beta-lactamase activity, cell wall biosynthesis, efflux pumps, and virulence factors.

The findings suggest that Solanum xanthocarpum methanol fruit extract has promising potential as a natural remedy against AMR associated with MRSA.

As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of action has not yet been clarified.

This study reviews the current status and characteristics of network pharmacology research in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese medicine treatment of the disease.

This study was searched on the Web of Science and PubMed using keywords, such as “traditional Chinese medicine”, “liver cancer,” and “network pharmacology.” The citation dates of the literature cited in this review are from 2000 to 2024.

The discovery of the key molecular mechanisms of traditional Chinese medicine in the treatment of liver cancer through the network pharmacology approach and the in-depth study of the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese medicine.

Network pharmacology research plays a key role in the treatment and prevention of liver cancer and deserves deeper exploration in the future.

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.

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.

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.

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.