Study on Dual Inhibitors of HIV‐1 IN/CCR5 Caffeoyl Derivatives as Neuroprotective Agents

Abstract

(E)‐3,4‐diacetoxystyryl aralkyl ketone and sulfone derivatives, with the skeleton of CAPE, were reported as dual inhibitors of HIV‐1 IN/CCR5 in our previous study. CAPE could show multifunctional neuroprotective properties through its antioxidant and anti‐inflammatory effects. In this study, neuroprotective effects of these dual inhibitors were evaluated, and the biological results revealed that the reduction of conjugated double bonds in ketones did not significantly influence their antioxidant and anti‐inflammatory effects. In addition, unsaturated ketones displayed better anti‐inflammatory activities than corresponding sulfones. Sulfone compounds 11 b and 11 d had the best antioxidant effects among all these compounds. Overall, most of these HIV‐1 dual inhibitors exhibited both antioxidant and anti‐inflammatory activities, and thus had the potential to reduce the morbidity of HIV‐associated neurocognitive disorders.

The Role of Catechol in Caffeic Acid Phenethyl Ester Derivatives for Neuroprotective Effects

“…The level of NO production reflects the degree of inflammation, and evaluating the inhibitory effect of NO production is a valuable strategy for measuring the anti‐inflammatory activities of target compounds. Lipopolysaccharide (LPS) has been reported to activate BV2 microglial cells to release NO, which can be used in the model of evaluating anti‐inflammatory effects [15d,18b] …”