Due to the overuse of antibiotics, bacterial resistance has markedly increased to become a global problem and a major threat to human health. Fortunately, in recent years, various new antibiotics have been developed through both improvements to traditional antibiotics and the discovery of antibiotics with novel mechanisms with the aim of addressing the decrease in the efficacy of traditional antibiotics. This manuscript reviews the antibiotics that have been approved for marketing in the last 20 years with an emphasis on the antibacterial properties, mechanisms, structure–activity relationships (SARs), and clinical safety of these antibiotics. Furthermore, the current deficiencies, opportunities for improvement, and prospects of antibiotics are thoroughly discussed to provide new insights for the design and development of safer and more potent antibiotics.

Objectives: This research sought to examine the impact of gossypol on cervical cancer tumors that have been transplanted subcutaneously in nude mice, as well as the associated risk of liver damage and its underlying mechanisms. Methods: A subcutaneous cervical cancer tumor model was established in nude mice using the cell suspension inoculation method. Tumor volume and morphological changes in various organs were observed, and the serum concentrations of IL-6, IL-10, and TNF-α were assessed. Protein expression was analyzed using Western blotting. Untargeted metabolomics was employed to identify differential metabolites in mouse liver tissues. Network toxicology was utilized to pinpoint common targets associated with gossypol and hepatotoxicity, followed by KEGG and GO enrichment analyses. Molecular docking was conducted to preliminarily explore the mechanisms underlying gossypol-induced liver injury. Results: Gossypol significantly suppressed the development of subcutaneous cervical cancer tumors in immunodeficient mice. The Western blotting technique results revealed that increasing doses of gossypol led to a reduction in the expression levels of PIK3R2, GRB2, and MAPK1, compared to the model group (p < 0.05). Untargeted metabolomics revealed 1464 metabolites, from which 9 distinct metabolites were selected for further analysis. Network toxicology results indicated that the hepatotoxicity-related targets of gossypol included MTOR, TNF, CASP3, BCL2L1, and BCL2. KEGG analysis suggested that the toxic mechanisms may be linked to pathways involved in malignancy, the HIF-1 signaling pathway, proteoglycans in cancer, apoptosis, and others. Conclusions: Gossypol demonstrates a significant therapeutic effect against cervical cancer; however, its hepatotoxicity risk, mediated through multiple targets and pathways, requires further investigation.

Melanoma is a highly aggressive malignancy characterized by strong invasive and metastatic potential. CPEB4 has been implicated in melanoma progression and may serve as a potential therapeutic target. Alkannin has previously been reported to exert antitumor activity against melanoma; however, its in vivo efficacy and direct molecular interaction with CPEB4 remain unclear. In this study, a subcutaneous xenograft model using BALB/c nude mice was used to assess the in vivo antitumor effects of alkannin, and CPEB4 expression was analyzed via Western blotting. DARTS, CETSA, and SPR investigations were used to elucidate the interaction between alkannin and CPEB4. In addition, stable CPEB4-knockdown A375 melanoma cells were established to examine the effects of alkannin on cell proliferation, apoptosis, cell cycle progression, migration, invasion, and downstream signaling molecules. Alkannin markedly suppressed tumor growth in the xenograft model and reduced CPEB4 expression in a dose-dependent manner compared with the model group. DARTS and CETSA demonstrated alkannin-induced stabilization of CPEB4, while SPR analysis using purified recombinant CPEB4 showed a direct physical interaction with alkannin, with micromolar affinity. At the molecular level, alkannin downregulated CPEB4 and PRC1 expression (p < 0.05), whereas CPEB4 knockdown markedly suppressed MITF and PRC1 (p < 0.05). Notably, alkannin treatment alone did not significantly alter MITF protein expression under the present experimental conditions. Alkannin exerts antitumor activity against melanoma, while its interaction with CPEB4 and the associated molecular changes may contribute to cellular responses involving proliferation, survival, migration, invasion-related phenotypes, and mitotic regulation.