Background: Chalcones are naturally occurring compounds found in various plant species which are
widely used for the traditional popular treatments. Chalcones are distinguished secondary metabolites reported
to display diverse biological activities such as antiviral, antiplatelet, anti-inflammatory, anticancer, antibacterial
and antioxidant. The presence of a,ß-unsaturated carbonyl group in chalcones is assumed to be responsible for
their bioactivity. In addition, heterocyclic compounds having nitrogen such as isoquinolines are of considerable
interest as they constitute the core structural element of many alkaloids that have enormous pharmacological
Objective: The objective of this study is the synthesis and biological activity of novel chalcones incorporating
thiadiazolyl isoquinoline as potential anticancer candidates. Different genetic tools were used in an attempt to
know the mechanism of action of this compound against breast cancer.
Methods: An efficient one pot synthesis of novel chalcones incorporating thiadiazolyl isoquinoline was
developed. The cytotoxic activity of the novel synthesized compounds was performed against four different
kinds of cancer cell lines.
Results: Among all the tested derivatives, chalcone 3 has the best cytotoxic profile against A549, MCF7, and
HeLa cell lines, with IC50s values 66.1, 51.3, and 85.1μM, respectively. Molecular docking studies for chalcone
3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while
tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding.
Conclusion: We have developed an efficient method for the synthesis of novel chalcones incorporating thiadiazolyl
isoquinoline. All compounds showed better cytotoxicity results against four kinds of cancer cell lines
(A549, MCF7, HCT116, and HELA cells). The results depicted that chalcone 3 has a high and promising cytotoxic
effect against HELA cell line and the mechanism of cytotoxicity was widely studied through different
theoretical and experimental tools. Thus, the newly synthesized derivative 3 can be utilized as a novel chemotherapeutic
compound for cervical carcinoma.