European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2018-01-10 , DOI: 10.1016/j.ejmech.2018.01.030 Yu-Zhuo Wu , Hua-Wei Zhang , Zhao-Hui Sun , Jun-Gui Dai , You-Cai Hu , Rui Li , Peng-Cheng Lin , Gui-Yang Xia , Ling-Yan Wang , Bo-Lin Qiu , Jing-Fang Zhang , Guang-Bo Ge , Sheng Lin
Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1–3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64 μg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC50 value of 2.01 μM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2.
中文翻译:
Bysspectin A,一种异常的八肽二聚体和内生真菌Byssochlamys spectabilis IMM0002的前体衍生物及其生物学活性
Bysspectin A(1),聚酮化合物衍生的具有新颖的碳骨架octaketide二聚体,和两个新的前体衍生物,bysspectins B和C(2和3),从的内生真菌的有机提取物中获得丝衣霉壮观已被分离从传统中药植物Edgeworthia chrysantha的叶子组织中提取,再加上已知的octaketide,paecilocin A(4)。它们的结构通过HRMS,1D和2D NMR光谱分析确定。提出了它们生物合成途径的可行途径。化合物1 - 3对其抗菌活性进行了测试。只有化合物3对大肠杆菌和金黄色葡萄球菌的活性较弱,MIC值分别为32和 64μg / mL。此外,评价了化合物1和4对人羧酸酯酶(hCE1,hCE2)的抑制作用。结果表明,bysspectin A(1)是一种新型且高度选择性的hCE2抑制剂,IC 50值为2.01μM 。对接模拟还表明,活性化合物1通过氢键与hCE2的Ser-288(催化腔中的催化氨基酸)相互作用,揭示了其对hCE2的高度选择性抑制作用。