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Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried out a high throughput screening and identified compound 4 as a moderate DRAK2 inhibitor with an IC50value of 3.15?μM. Subsequent SAR studies of hit compound 4 led to the development of novel benzofuran-3(2H)-one series of DRAK2 inhibitors with improved potency and favorable selectivity profiles against 26 selected kinases. Importantly, most potent compounds 40 (IC50?=?0.33?μM) and 41 (IC50?=?0.25?μM) were found to protect islet β-cells from apoptosis in dose-dependent manners. These data support the notion that small molecule inhibitors of DRAK2 represents a promising strategy for the treatment of diabetes.

A series of aurones were prepared from various phenols via phenoxy acetic acids and coumaranones and evaluated for insect antifeedant activity against the common cutworm (Spodoptera litura). The naturally occurring aurone was most active at an ED50 of 0.12 μmol/cm2. The synthetic precursor, coumaranones, showed that the introduction of methoxyl and methyl groups to the benzene ring increased insect antifeedant activity. Similarly, the tested aurones showed that the introduction of methoxyl group to the A and/or B rings increased the insect antifeedant activity, but 4,5,6- and 3 ,4 ,5 -trisubstituted compounds did not show this activity in this test. The hydroxylation of aurones in the B ring should be disadvantageous for insect antifeedant activity against S. litura. Although the melting points did not correlate well with the insect antifeedant activity, compounds that were nearly inactive had high melting points. A significant correlation was noted between biological activity (pED50) and a hydrogen-bonding parameter calculated from the Rf value obtained from SiOH thin-layer chromatography and a lipophilicity parameter (log k) calculated from the retention time in ODS high-performance liquid chromatography. The respective correlation coefficients (r) were -0.83 and -0.70. The introduction of alkoxy and alkyl groups along with adequate hydrogen bonding seems to contribute to the antifeedant activity of the compounds tested.