Design, Synthesis, and Biological Evaluation of 4‐Phenoxyquinoline Derivatives Containing Benzo[<i>d</i>]thiazole‐2‐yl Urea as c‐Met Kinase Inhibitors

Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential.Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold-based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture-based derivatives as potent anticancer agents.

show abstract

“…Lei et al [75] have reported phenoxyquinoline-bearing benzothiazole derivatives as potent anticancer agents. Compound…”

Section: Benzothiazole Scaffold-bearing Derivatives As Potent Anticancer Agentsmentioning

confidence: 99%

Advances in 2‐substituted benzothiazole scaffold‐based chemotherapeutic agents

Haider

Rehman

Pathak

et al. 2021

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

Benzothiazole derivatives in the design of antitumor agents

Paoletti,

Supuran

2024

Archiv der Pharmazie

View full text Add to dashboard Cite

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.

show abstract