Natural products are the fundamentals of drug discovery due to their exceptional structural diversity and biological activity’s evolutionary optimization. The review provides a critical and integrative analysis of natural products in pharmaceutical chemistry, highlighting their significance for current biomedicine and pharmacotherapy. The review is organized around a system that connects structure, function, and translation, focusing on structural analysis, scaffold design, and mechanistic understanding in major disease-relevant therapeutic areas. Investigations on representative compounds like paclitaxel, artemisinin, and curcumin are presented to explain the way molecular architecture regulates pharmacological activity, drug selectivity, and clinical performance. The review evaluates significant medicinal chemistry strategies, including semisynthetic modification, prodrug design, and scaffold optimization, and their crucial roles in enhancing potency, pharmacokinetics, and safety. We critically examine the latest advancements in drug delivery technologies, particularly those based on nanotechnology and carrier-free methods, regarding their translational potential and regulatory concern. Current challenges pertaining to pharmacokinetics and ADMET properties, as well as the standardization of analysis, are also examined, emphasizing their impact on reproducibility in research. Researchers investigate the role and limitations of emerging fields such as genome mining, synthetic biology, and network pharmacology in enhancing discovery pipelines. Thus, this review integrates chemical, pharmacological, and translational approaches and suggests an effective strategy to overcome challenges in the development of natural products as the next generation of precision medicine therapeutic agents.

Introduction: Glioblastoma (GBM) is a high-grade primary brain tumor with a high proliferation rate, metabolic reprogramming, and unresponsiveness to existing therapeutic interventions. One of the most important glycolytic enzymes is pyruvate kinase M2 (PKM2), which plays two roles in GBM: controlling tumor metabolism and nuclear gene expression. The complexity of PKM2 functions is important in the formulation of effective targeted treatments against GBM. Methods: A comprehensive search of electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar was conducted from inception until 2025. The keywords used were PKM2, glioblastoma, cancer metabolism, and therapeutic targeting. The screening and selection of studies were based on their relevance to the molecular biology of PKM2, its metabolic and nuclear functions, and GBM therapeutic approaches. Results: The outcomes show that PKM2 enhances the Warburg effect in GBM, maintaining glycolytic flux and biosynthetic pathways that support tumor growth under hypoxic conditions. Moreover, PKM2 is associated with proliferation-, stemness-, and immune-evasion-related gene expression. Small-molecule activators and inhibitors, RNA-based therapies, and advanced drug-delivery systems that bypass the blood-brain barrier are therapeutic approaches for targeting PKM2. Medicinal chemistry initiatives have optimized PKM2 modulators, but challenges remain regarding isoform selectivity and effective brain penetration. Discussion: The discussion of PKM2 reveals that it has both metabolic and nuclear functions, making it a promising therapeutic target. However, the difficulties in specific targeting and delivery require combined solutions using molecular, pharmacological, and nanotechnological methods. Conclusion: In general, the bifunctional metabolic and nuclear characteristics of PKM2 indicate its relevance as a therapeutic target in glioblastoma, suggesting that combined approaches are needed to support clinical translation.

Green tea contains a bioactive polyphenol called epigallocatechin gallate (EGCG), which may be used as a therapeutic agent for breast cancer (BC). This review examines the pharmacological and chemical properties of EGCG, which may make it a valuable therapeutic agent for treating breast cancer. The distinctive physicochemical characteristics of EGCG, such as its solubility, stability, and bioavailability, are based on its molecular structure, which is also crucial for its medicinal uses. Furthermore, the availability of EGCG as a naturally occurring substance, its production in "Camellia sinensis," and the use of sophisticated extraction methods are also covered. Apoptosis is induced via caspase activation and mitochondrial failure. Metastasis-related enzymes are inhibited, and key signaling pathways, including PI3k, Akt, and MAPK, are modulated as part of EGCG's multifaceted anti-cancer actions. The synergistic benefits of EGCG with traditional chemotherapies, in combating drug resistance and enhancing their effectiveness, significantly improve the therapeutic value of these treatments. Limited bioavailability is addressed via liposomal delivery, nanoparticle encapsulation, and structural optimisation. Pharmacokinetics, toxicology, and clinical studies all support its safety and effectiveness. This study highlights the promise of EGCG as a therapeutic agent for breast cancer, exploring its molecular interactions, new formulations, and the integration of chemistry and molecular mechanisms to enhance EGCG's therapeutic applicability in clinical settings.

Fungal infections are an increasing global health concern, especially in individuals with weakened immune systems. Their complexity stems from intricate interactions between fungal pathogens and host cells, making diagnosis and treatment difficult. Although advances have been made, key aspects of host–pathogen interactions, such as invasion mechanisms, immune evasion, and variable host responses, remain unclear. Systems biology provides a holistic way to study these processes by integrating large-scale data on genes, proteins, metabolites, and immune pathways. Multiomics approaches, including genomics, transcriptomics, proteomics, metabolomics, and immunomics, offer deeper insight into the molecular events during infection. Integrating these datasets reveals pathways involved in infection progression, host immunity, and pathogen clearance. This chapter highlights how multiomics-driven systems biology enhances understanding of fungal pathogenicity, immune dysregulation, and host defense, supporting the development of improved therapeutic strategies.

Introduction: PELP1 is an oncogenic scaffold protein characterized by proline-, glutamic acid-, and leucine-rich domains, and serves as a crucial coregulator of the estrogenic receptor (ER). It facilitates tumour growth, metastasis, and a worse prognosis in ER+ breast cancer. This review examines PELP1 expression, prognostic relevance, and therapeutic potential, integrating prior studies to underscore its clinical importance. Methods: This systematic review includes publications from 2014–2024, retrieved via database searches using keywords like “PELP1,” “ER-positive breast cancer,” and “PELP1 expression” on PubMed, Google Scholar, and ScienceDirect. Articles were selected based on their relevance to PELP1 expression and its correlation with tumour behaviour and survival outcomes in ER+ breast cancer. Results: Six studies were identified that investigated the correlation between PELP1 levels and breast cancer outcomes. Findings suggest that elevated PELP1, particularly in the NH2 region, is associated with larger tumours, higher grade, and poorer prognosis. A statistical link was found between high PELP1 expression and elevated estrogen levels in ER+ tumours. However, small sample sizes and the absence of validation cohorts limit the conclusion. Discussion: Evidence suggests that PELP1 enhances ER signaling and may contribute to endocrine resistance. Its dual genomic and non-genomic roles underline its potential as a biomarker and therapeutic target. Conclusion: Although preliminary findings may indicate that PELP1 has the potential to be a clinically useful biomarker and therapeutic target for ER+ breast cancer, the current studies fail to sufficiently demonstrate that PELP1 is clinically beneficial. There is a need for more research with larger, more reliable group samples and more involved mechanistic studies.

Metabolic reprogramming is a defining feature of cancer that facilitates unregulated proliferation, adaptation to stress, and therapeutic resistance. Pyruvate kinase M2 (PKM2), a crucial glycolytic isoform, links cancer-causing signaling pathways to metabolic control and has become both a biomarker and a therapeutic target. In addition to its catalytic role, PKM2 regulates gene expression, immune evasion, and hypoxia adaptation, placing it at the intersection of multiple cancer hallmarks. This review integrates structural, biochemical, and functional evidence to analyze PKM2's involvement in tumor proliferation, therapeutic resistance, and its modulation by both natural and synthetic agents, including shikonin and metformin. Preclinical studies show that targeting PKM2 can reduce glycolytic flux, make tumor cells more sensitive to chemotherapy, and slow tumor growth. Nonetheless, clinical translation remains difficult due to resistance mechanisms, limited selectivity, off-target effects, low bioavailability, and expression in normal proliferating tissues. Recent advancements in multi-omics profiling and drug design offer opportunities to overcome these obstacles through more selective modulators, biomarkerdriven patient stratification, and rational combination therapies. This review critically assesses the potential and constraints of PKM2, highlighting translational challenges and future research priorities to establish PKM2 as a clinically significant target in precision oncology.