Title:A Review on the Design, Synthesis, and Structure-activity Relationships of
Benzothiazole Derivatives against Hypoxic Tumors
Volume: 19
Issue: 7
Author(s): Akif Hakan Kurt, Lokman Ayaz, Furkan Ayaz, Zeynel Seferoglu and Yahya Nural*
Affiliation:
- Department of Analytical Chemistry, Faculty of Pharmacy, Mersin University,
Mersin, 33169, Turkey
- Advanced Technology, Research and Application Center, Mersin University, 33343 Mersin,
Turkey
Keywords:
Anti-cancer activity, benzothiazole, heterocyclic compounds, hypoxia, organic synthesis, brain tumors.
Abstract: There has been a growing body of studies on benzothiazoles and benzothiazole derivatives
as strong and effective anti-tumor agents against lung, liver, pancreas, breast, and brain
tumors. Due to the highly proliferative nature of the tumor cells, the oxygen levels get lower than
that of normal tissues in the tumor microenvironment. This situation is called hypoxia and has
been associated with increased ability for carcinogenesis. For the drug design and development
strategies, the hypoxic nature of the tumor tissues has been exploited more aggressively. Hypoxia
itself acts as a signal initiating system to activate the pathways that eventually lead to the spread
of the tumor cells into the different tissues, increases the rate of DNA damage, and eventually
ends up with more mutation levels that may increase the drug resistance. As one of the major
mediators of hypoxic response, hypoxia-inducible factors (HIFs) have been shown to activate
angiogenesis, metastasis, apoptosis resistance, and many other protumorigenic responses in cancer
development. In the current review, we will be discussing the design, synthesis, and structureactivity
relationships of benzothiazole derivatives against hypoxic tumors such as lung, liver,
pancreas, breast, and brain as potential anti-cancer drug candidates. The focus points of the study
will be the biology behind carcinogenesis and how hypoxia contributes to the process, recent
studies on benzothiazole and its derivatives as anti-cancer agents against hypoxic cancers, conclusions,
and future perspectives. We believe that this review will be useful for researchers in the
field of drug design during their studies to generate novel benzothiazole-containing hybrids
against hypoxic tumors with higher efficacies.