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

• Published in: Marine drugs Vol. 18; no. 9; p. 479
• Main Authors: Guo, Xing-Chen, Zhang, Ya-Hui, Gao, Wen-Bin, Pan, Li, Zhu, Hua-Jie, Cao, Fei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.09.2020; MDPI AG
• Subjects: bioactivity; Cell Line, Tumor; cell lines; chitinase; Chitinases - antagonists & inhibitors; Circular Dichroism; circular dichroism spectroscopy; cytotoxicity; diketopiperazine; diketopiperazines; Diketopiperazines - chemistry; Diketopiperazines - isolation & purification; Diketopiperazines - pharmacology; drugs; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; fungi; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Magnetic Resonance Spectroscopy; marine-derived fungus; metabolites; nuclear magnetic resonance spectroscopy; Penicillium; Penicillium - metabolism; Penicillium polonicum; Prazosin - analogs & derivatives; probability; quinazoline; Quinazolines - chemistry; Quinazolines - isolation & purification; Quinazolines - pharmacology; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; quinazoline; Penicillium polonicum; bioactivity; marine-derived fungus; diketopiperazine
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md18090479

Three new quinazoline-containing diketopiperazines, polonimides A–C (1–3), along with four analogues (4–7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1–3 were 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 in 3 and 5. All of 1–7 were tested for their chitinase inhibitory activity against OfHex1 and OfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1–7 exhibited weak activity towards OfHex1 and strong activity towards OfChi-h at a concentration of 10.0 μM, with the inhibition rates of 0.7%–10.3% and 79.1%–95.4%, respectively. Interestingly, 1–7 showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.