Study on Dual Inhibitors of HIV‐1 IN/CCR5 Caffeoyl Derivatives as Neuroprotective Agents. Issue 22 (12th June 2018) - Hao, Yameng
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. Abstract : HIV‐associated neurocognitive disorders (HAND) could affect 50% of HIV patients as complications of AIDS, which has not attracted much attention for drug design. We evaluated neuroprotective effects of our HIV inhibitors based on pathogenic mechanisms of HAND, and the results revealed that our HIV inhibitors had potential to act as neuroprotective agents and reduce HAND through both anti‐HIV and neuroprotective effects.