Anti-Cancer Agents in Medicinal Chemistry - Online First

Natural products and their derivatives have played a dominant role in the development of therapeutic agents. Traditionally, most of the natural products developed for the effective treatment of different diseases have been sourced from plants. Natural product discovery has seen a shift of focus towards microorganisms due to the chemical diversity of bioactive products they synthesize. Myxobacteria produce a large variety of novel chemical entities with diverse structures and varied bioactivities. In the last few decades, secondary metabolites from different genera of myxobacteria have been recognized as harbouring potent anticancer activity. Several analogs of these anticancer compounds have been prepared to address the limitations such as, poor solubility, high toxicity and low production yield, in order to obtain the compounds in higher quantities with better pharmacological properties and target selectivity. For example, a semi-synthetic derivative of epothilone obtained from a strain of myxobacterium has been approved for clinical use against taxane-resistant breast cancer. The anticancer compounds from myxobacteria target microtubules, the cytoskeleton, vacuolar ATPase, methionine aminopeptidase, exportin, the proteasome or translation elongation factor to exert anticancer activity. The focus of this review is on the promising anticancer compounds produced by myxobacteria, their targets and their mechanisms of action in cancer cells.

Chimeric Antigen Receptor T-cell (CAR-T) therapy represents a pioneering advancement in immunotherapy, demonstrating substantial clinical success in the treatment of hematologic malignancies, particularly in B-cell hematologic malignancies. This therapeutic approach involves the genetic modification of a patient's T-cells to express receptors specific to tumor antigens, thereby enabling the CAR T-cells to identify and eradicate tumor cells, which significantly enhances the patient's treatment prognosis. Despite the remarkable efficacy of CAR-T therapy, concerns regarding its safety have emerged during clinical implementation. Notably, research has indicated that CAR T-cell therapy may be associated with the development of secondary primary malignancies, prompting considerable apprehension within the clinical community regarding the long-term adverse effects of this treatment modality. This article aims to investigate the potential mechanisms responsible for the induction of secondary primary malignancies by CAR T-cells, evaluate the associated risk factors, and discuss therapeutic strategies to mitigate this issue. Furthermore, the article will explore future research directions focused on optimizing the safety profile of CAR-T therapy, thereby providing a theoretical foundation for the development of safer and more effective therapeutic interventions.

Natural coumarins, a class of compounds found abundantly in various plants, are emerging as promising candidates in fight against cancer. Their ability to target multiple cancer-related processes has drawn significant interest from researchers. Natural coumarins exhibit anticancer effects through mechanisms such as inducing apoptosis, which is the programmed death of cancer cells, inhibiting cell proliferation, and disrupting angiogenesis, the process by which tumors develop their own blood supply to sustain growth. What makes coumarins particularly intriguing is their broad-spectrum activity against various types of cancer cells, from breast to lung to colon cancers. They interact with key molecular pathways that drive tumor progression, making them versatile agents in cancer therapy. Additionally, unlike many conventional chemotherapy drugs, natural coumarins generally have lower toxicity, which could translate to fewer side effects for patients. This characteristic makes them attractive as potential standalone treatments or as complementary therapies that enhance the efficacy of existing drugs while minimizing harm to normal cells. Ongoing research continues to explore the therapeutic potential of natural coumarins to better understand their full therapeutic potential and how they might work in combination with other anticancer agents. As the body of evidence grows, these natural compounds could become integral components of more effective and less harmful cancer treatment regimens, offering new hope for patients facing this challenging disease. This review was conducted by systematically analyzing the existing literature on natural coumarins and their anticancer potential.

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutation is commonly found in colorectal, lung, and pancreatic carcinomas. Unfortunately, blocking KRAS straight away has proven to be challenging. PROTACs (Proteolysis Targeting Chimeras), a class of bifunctional molecules, are designed to break down proteins, offering a unique strategy to target KRAS and overcome the limitations of traditional inhibition. This review discusses PROTACs targeting KRAS mutations in cancer, highlighting major findings, current limitations, and future perspectives. The review was performed using the databases, namely, Medline, Embase, Science Direct, and Scopus, using the keywords “PROTACs, protein degradation, anti-tumor action, cancer treatment, KRAS mutation”. Additional information was gathered from related textbooks, reviews, and documents. PROTAC treatment results in the suppression of downstream signalling pathways associated with KRAS, such as the MAPK and PI3K/AKT pathways. Animal studies demonstrate the ability of the PROTAC to effectively target KRAS-mutant tumors, inhibiting tumour growth without significant toxicities. New advances in this field can lead to cancer treatments that specifically target KRAS-mutant tumors.