1 research outputs found
Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation
Breast cancer is currently the most commonly diagnosed
cancer,
with 287,850 new cases estimated for 2022 as reported by the American
Cancer Society. Therefore, finding an effective treatment for this
disease is imperative. Chalcones are α,β-unsaturated systems
found in nature. These compounds have shown a wide array of biological
activities, making them popular synthetic targets. Chalcones consist
of two aromatic substituents connected by an enone bridge; this arrangement
allows for a large number of derivatives. Given the biological relevance
of these compounds, novel ferrocene-heterocycle-containing chalcones
were synthesized and characterized based on a hybrid drug design approach.
These heterocycles included thiophene, pyrimidine, thiazolyl, and
indole groups. Fourteen novel heterocyclic ferrocenyl chalcones were
synthesized and characterized. Herein, we also report their cytotoxicity
against triple-negative breast cancer cell lines MDA-MB-231 and 4T1
and the noncancer lung cell line MRC-5. System 3 ferrocenyl chalcones
displayed superior anticancer properties compared to their system
1 analogues. System 3 chalcones bearing five-membered heterocyclic
substituents (thiophene, pyrazole, pyrrole, and pyrimidine) were the
most active toward the MDA-MB-231 cancer cell line with IC50 values from 6.59 to 12.51 μM. Cytotoxicity of the evaluated
compounds in the 4T1 cell line exhibited IC50 values from
13.23 to 213.7 μM. System 3 pyrazole chalcone had consistent
toxicity toward both cell lines (IC50 ∼ 13 μM)
as well as promising selectivity relative to the noncancer MRC-5 control.
Antioxidant activity was also evaluated, where, contrary to anticancer
capabilities, system 1 ferrocenyl chalcones were superior to their
system 3 analogues. Antioxidant activity comparable to that of ascorbic
acid was observed for thiophene-bearing ferrocenyl chalcone with EC50 = 31 μM