Anti-Cancer Agents in Medicinal Chemistry - Online First

Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chemistry for their structural diversity and biological activity. However, their therapeutic potential is often hindered by low bioavailability, poor solubility, and rapid metabolism. Metal complexation has emerged as a promising solution, with pyridine nitrogen serving as an excellent coordination site for transition metals. These pyridine-metal complexes enhance stability, bioavailability, and anticancer properties, exhibiting potent cytotoxicity through mechanisms like ROS generation, DNA intercalation, and apoptosis induction. This review highlights the latest progress (2022-2024) in the field, emphasizing the structural modifications, and mechanistic insights that have propelled pyridine-metal complexes as potent anticancer agents. Special attention is given to the role of metal complexation in enhancing the anticancer potency of pyridine derivatives, with examples of preclinical studies showing their efficacy against various cancer types. The findings emphasize the potential of pyridine-metal complexes as a transformative approach in oncology, bridging the gap between innovative chemical design and impactful therapeutic applications.

Cancer, with a high incidence and mortality rate, has emerged as a major public health problem worldwide. Currently, new approaches, such as targeted therapy and immunotherapy, are giving hope to patients. However, drug resistance and adverse side effects are major barriers to cancer treatment. As a result, there is a greater focus on the development of cancer therapy strategies and medications with low toxicity and high efficacy. Cryptotanshinone (CTS), a diterpenoid quinone extracted from Salvia miltiorrhiza Bunge, exhibits a wide range of biological activities, including immunomodulatory, anti-inflammatory, and antitumor effects. In recent years, numerous studies have highlighted its significant antitumor properties, indicating potential clinical applications and development value. However, the clinical use of cryptotanshinone has been limited due to its poor water solubility and low bioavailability. To overcome these limitations, researchers are exploring new drug delivery systems, and novel formulation systems based on nanotechnology are being developed to improve the delivery and effectiveness of cryptotanshinone. In this review, we aim to consolidate the existing knowledge regarding the antitumor effects of cryptotanshinone and emphasize the latest advancements in its nanoformulation development. We hope to provide insights that will further improve the antitumor efficacy and clinical applicability of cryptotanshinone.

Tumor-infiltrating immune cells (TIICs) have been identified as critical components in the development of cancer drug resistance. This review aims to discuss the various types of TIICs, such as macrophages and T cells, that have been linked to cancer drug resistance. Furthermore, we explore the mechanisms by which TIICs contribute to drug resistance and how these mechanisms may differ across various tumor types. Additionally, we examine the potential of immune checkpoint inhibitors in combination with traditional cancer therapies as a strategy to overcome TIIC-mediated cancer drug resistance. In conclusion, this review provides an in-depth analysis of the current knowledge on the role of TIICs in cancer drug resistance and highlights potential avenues for future research to develop more effective treatment strategies. The findings presented in this review emphasize the importance of understanding the complex interactions between cancer cells and the immune system in order to develop novel therapeutic approaches that can overcome TIIC-mediated cancer drug resistance.

The alternative splicing (AS) of pre-mRNA is an important process in controlling the expression of human genes, which can enrich the diversity of the proteome and regulate gene function. On the contrary, aberrant splicing contributes significantly to numerous human diseases progression, including tumors, neurological diseases, metabolic diseases, infections, and immune diseases. The PUF60, a protein related to RNA splicing, plays critical functions in RNA splicing and gene transcription regulation. In addition, it can achieve synergistic binding with U2AF65 on RNA through interactions in the pyrimidine region, promoting the splicing of introns with weak 3'- splice sites and pyrimidine bundles. Nevertheless, an increasing amount of evidence supports that it shows a significant overexpression pattern in the vast majority of cancer cells and is crucial for embryonic development, indicating that PUF60 may hold the post of a potential therapeutic target for such diseases. These studies have significantly increased our interest in PUF60. Thus, we briefly reviewed the structural domain characteristics of the PUF60, splicing mutants of PUF60, and the roles and functions in human diseases, including various cancers, infections of bacterium and viruses, myositis, and Verheij syndrome. Furthermore, the targeted PUF60 inhibitors and boundedness of the current research were elaborated on in the article. The article effectively communicates critical perception and insight, making it a precious resource for those interested in PUF60 research and treatment.