Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived FungusPenicillium polonicum

Three new quinazoline-containing diketopiperazines, polonimides A-C (1-3), along with four analogues (4-7), were obtained from the marine-derived fungusPenicillium polonicum. Among them,2and4,3and5were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of1-3were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in3and5. All of1-7were tested for their chitinase inhibitory activity againstOfHex1 andOfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds1-7exhibited weak activity towardsOfHex1 and strong activity towardsOfChi-h at a concentration of 10.0 mu M, with the inhibition rates of 0.7%-10.3% and 79.1%-95.4%, respectively. Interestingly,1-7showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.