Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.
Department of Natural Products Research, Osaka University of Pharmaceutical Sciences, Nasahara 4-20-1, Takatsuki, Osaka 569-1094, Japan.
Mar Drugs. 2020 Apr 20;18(4):221. doi: 10.3390/md18040221.
Inspired by the significant -glucosidase inhibitory activities of (+)- and (-)-pericosine E, we herein designed and synthesized 16 analogs of these marine natural products bearing a methoxy group instead of a chlorine atom at C6. Four of these compounds exhibited moderate -glucosidase inhibitory activities, which were weaker than those of the corresponding chlorine-containing species. The four compounds could be prepared by coupling reactions utilizing the (-)-pericosine B moiety. An additional in silico docking simulation suggested that the reason of reduced activity of the C6-methoxylated analogs might be an absence of hydrogen bonding between a methoxy group with the surrounding amino acid residues in the active site in -glucosidase.
受 (+)-和 (-)-海鞘素 E 的显著α-葡萄糖苷酶抑制活性的启发，我们设计并合成了这些海洋天然产物的 16 个类似物，这些类似物在 C6 位上用甲氧基取代了氯原子。其中四种化合物表现出中等的α-葡萄糖苷酶抑制活性，比相应的含氯化合物弱。这四种化合物可以通过 (-)-海鞘素 B 部分的偶联反应来制备。另外的计算机对接模拟表明，C6-甲氧基化类似物活性降低的原因可能是在α-葡萄糖苷酶的活性部位，甲氧基与周围氨基酸残基之间不存在氢键。
