Liang Guang, Yang Shu-Lin, Shao Li-Li, Zhao Cheng-Guang, Xiao Jian, Lv Yan-Xia, Yang Ju, Zhao Yu, Li Xiao-Kun
School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
J Asian Nat Prod Res. 2008 Sep-Oct;10(9-10):957-65. doi: 10.1080/10286020802181257.
Curcumin is an excellent lead compound with a variety of bioactivity. Recent articles reported that curcumin's instability and low bioavailability in vivo are mainly due to its easily decomposable beta-diketone moiety. With the aim of bioactive curcumin analogs with better pharmacokinetic property, we present here 11 bis(arylmethenyl)cyclopentanones similar to curcumin and without beta-diketone moiety by reacting relevant arylaldehydes and cyclopentanones. The analogs were structurally determined by 1HNMR and MS spectra, and the crystal structure of 6 was analyzed by X-ray diffraction. Their antibacterial activities in vitro against seven Gram-positive and Gram-negative bacteria were tested, and their inhibition of TNF-alpha and IL-6 secretion in LPS-induced mouse macrophages was investigated using enzyme-linked immunosorbent assay. It was observed that several derivatives displayed higher activity when compared with curcumin, and most of the analogs exhibited activities against the ampicillin-resistant Gram-negative Enterobacter cloacae.
姜黄素是一种具有多种生物活性的优秀先导化合物。最近的文章报道，姜黄素在体内的不稳定性和低生物利用度主要归因于其易于分解的β-二酮部分。为了获得具有更好药代动力学性质的生物活性姜黄素类似物，我们在此通过使相关芳醛与环戊酮反应，展示了11种类似于姜黄素且不含β-二酮部分的双（芳基亚甲基）环戊酮。通过1HNMR和MS光谱确定了类似物的结构，并通过X射线衍射分析了6的晶体结构。测试了它们对七种革兰氏阳性和革兰氏阴性细菌的体外抗菌活性，并使用酶联免疫吸附测定法研究了它们对脂多糖诱导的小鼠巨噬细胞中TNF-α和IL-6分泌的抑制作用。观察到与姜黄素相比，几种衍生物表现出更高的活性，并且大多数类似物对耐氨苄青霉素的革兰氏阴性阴沟肠杆菌具有活性。
