Synthesis, Characterization, and DRAK2 Inhibitory Activities of Hydroxyaurone Derivatives

Abstract

We reported the synthesis of 25 derivatives of hydroxyaurone, which were characterized by 1 H NMR, 13 C NMR, high resolution mass spectrum, and single crystal X-ray diffraction analysis. Their activities on the death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) were evaluated by kinase detection kit at a dosage of 5 μM. Most of the synthetic hydroxyaurones exhibited moderate to good inhibitory activities. The IC50 value ranged from 0.81 to 2.42 μM when the structure of aurone's B ring was kept unchanged and its A ring was substituted by hydroxyl groups. On the contrary, modification of the aurone's B-ring with hydroxyl groups lead to the IC50 value ranging from 1.15 to 17.5 μM. This indicates presence of hydroxyl group of the B ring is crucial for aurone's DRAK2 kinase inhibitors. Therefore, hydroxyaurone may serve as a new possible lead compound for the discovery of DRAK2. Further pharmacological investigations are underway and will be reported in due course.

Intramolecular Dearomative Inverse-Electron-Demand Diels Alder Strategy for the Total Synthesis of (+)-Alstonlarsine A

“…In 2019, one such monoterpenoid indole alkaloid has been isolated from Alstonia scholaris and named alstonlarsine A ( 1 ), whose polycyclic skeleton has previously been unseen in nature: it consists of a 9-azatricyclo­[4.3.1.0 3,8 ]­decane unit condensed to the indoline ring (Figure ). Moreover, its biological activity is quite rareit is a micromolar range inhibitor of the Drak2 signaling molecule (relevant for T-cell activation), whose inhibition induces resistance to autoimmunity in mice, while not compromising the response of the immune system to viral or bacterial attack …”