Synthesis of chlorinated flavonoids with anti-inflammatory and proapoptotic
activities in human neutrophils
a b s t r a c t
Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as
therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity
of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated
products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in
neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated
flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than
their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetateactivated
neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-
dependent fashion. The present data showed that 8-chloro-30,40,5,7-tetrahydroxyflavone (4a) constitute
an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms
engaged at the onset and progression of inflammation.