Benzothiazole derivatives in the design of antitumor agents.
Niccolò PaolettiClaudiu T SupuranPublished in: Archiv der Pharmazie (2024)
Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti-inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor-hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual-specificity protein kinase, cyclin-dependent protein kinases, casein kinase 2, Rho-related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase-2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl-CoA desaturase, peroxisome proliferator-activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia-inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.
Keyphrases
- protein kinase
- cell cycle
- vascular endothelial growth factor
- growth factor
- signaling pathway
- epidermal growth factor receptor
- endothelial cells
- drug discovery
- heat shock
- tyrosine kinase
- public health
- cell proliferation
- anti inflammatory
- healthcare
- advanced non small cell lung cancer
- cancer therapy
- oxidative stress
- mental health
- emergency department
- papillary thyroid
- gene expression
- sensitive detection
- binding protein
- drug induced
- liver injury
- young adults
- risk assessment
- epithelial mesenchymal transition
- heat stress
- fatty acid
- squamous cell carcinoma
- quantum dots
- combination therapy
- health information
- health promotion