The
severity, prevalence, and complexity of cancer do not need any introduction at
present. The coumarin scaffold has been explored intermittently for its anti-cancer
potential for a long time, and continuous research is further in progress. The concept
of molecular hybridization has opened new doors towards the design and development
of therapeutic candidates, capable of binding to multiple targets. This has been
proven to be a promising approach for diseases with complex pathophysiology involving
a variety of targets. In this direction, several research groups have explored the
therapeutic potentials of coumarin and its derivatives against cancer. Coumarin
possesses multiple sites for substitution/tethering/fusion, providing ease for constructing
coumarin hybrid molecules. Coumarin and its derivatives have the ability to
exert anti-cancer activity by interacting/binding with several targets,
including aromatase, sulphatase, protein kinases, telomerase, carbonic
anhydrase, caspases, SERD (selective estrogen receptor downregulators),
tubulin, phosphoinositide 3- kinases (PI3K), topoisomerase and hormones. These
targets are involved in complex pathological events during the development of
cancer. Several heterocyclic moieties beyond coumarin are also capable of
binding to one or more of these targets. Therefore, conjuring such a
heterocycle with coumarin moiety is an ideal approach to target more than one
target simultaneously. In this chapter, the authors have highlighted important targets
along with their significance in the development of cancer. A description of reported
potent anti-cancer coumarin hybrids (in the past five years)
inhibiting/interacting with particular targets has been provided. Although
there is a tremendous advancement in developing hybrid molecules against
cancer, still no suitable candidate has been launched in the market for a long
time. So, further clinical and toxicological investigations on reported lead
molecules should be carried out on priority.
Keywords: Aromatase, Coumarin hybrids, PI3K, Protein kinase, SERD, Sulphatase, Targets.
