Mini Reviews in Medicinal Chemistry - Volume 25, Issue 8, 2025

The broad-spectrum action and capacity to target drug-resistant infections make synthetic Antimicrobial Peptides (AMPs) popular therapeutic agents. Indeed, the effective use of these peptides in clinical application relies on a thorough understanding of their Pharmacokinetic (PK) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics. Despite growing research on synthetic AMPs, there is a notable gap in the literature specifically addressing their ADMET profiles. Previous reviews have not extensively covered this area, providing a vital opportunity to study synthetic AMPs' pharmacokinetics and safety, which are crucial for their therapeutic development. This review covered research studies that focused on PK and ADMET of synthetic antimicrobial peptides from several databases, including Google Scholar, SCOPUS, PubMed, and Science Direct, within the years 2020 to 2024, and 12 related research papers have been found. AMPs display a wide range of PK behaviors, including rapid renal clearance, liver-centric distribution, broad distribution with low toxicity, high kidney retention, and gradual absorption with dose-dependent toxicity. Overall, the ADMET profiles of AMPs are crucial in assessing their therapeutic potential, and continuous study is necessary to enhance their practical feasibility. An in-depth investigation of the in vivo ADMET and pharmacokinetic profiles of synthetic AMPs is presented in this review to address the current gap in the research. The findings of this study provide important insights for developing synthetic AMPs as effective antimicrobial drugs.

Metabolic reprogramming is a hallmark of cancer. Distinct and unusual metabolic aberrations occur during tumor development that lead to the growth and development of tumors. Oncogenic signaling pathways eventually converge to regulate three major metabolic pathways in tumor cells i.e., glucose, lipid, and amino acid metabolism. Therefore, identifying and targeting the metabolic nodes of cancer cells can be a promising intervention and therapeutic strategy for patients with malignancies. The long road of new drug discovery for cancer therapy has necessitated relooking alternative strategies such as drug repurposing. Advanced genomic and proteomic technologies for the assessment of cancer-specific biological pathways have led to the discovery of new drug targets, which provide excellent opportunities for drug repurposing. The development of effective, safe, cheaper, and readily available anticancer agents is the need of the hour, and drug repurposing has the potential to break the current drug shortage bottleneck. This review will accordingly cover various metabolic pathways that are aberrant in cancer, and strategies for targeting metabolic reprogramming by using repurposed drugs.

Most natural products in nature have broad but not exceedingly good biological activities. The pyrazole structure has been introduced into natural products due to its suitability for various synthetic methods and its broad pharmacological activities. This article provides a detailed introduction to the anti-inflammatory, antibacterial, antifungal, antiviral, and anti-Alzheimer disease activities of pyrazole-modified natural product derivatives, particularly their anti-tumor activity. It is worth noting that compared to lead compounds, most natural product derivatives modified with pyrazole exhibit excellent pharmacological activity. Some of these derivatives exhibit outstanding anti-tumor activity, with IC50 values reaching nanomolar levels. This review provides more research directions and choices for future studies on natural products.