Bankeu Jean J K, Sattar Hira, Fongang Yannick S F, Muhammadi Syeda W, Simoben Conrad V, Ntie-Kang Fidele, Feuya Guy R T, Tchuenmogne Marthe A T, Lateef Mehreen, Lenta Bruno N, Ali Muhammad S, Ngouela Augustin S
Department of Chemistry, Faculty of Science, The University of Bamenda, P.O. Box 39, Bambili, Cameroon.
International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Nat Prod Bioprospect. 2019 Jan;9(1):49-59. doi: 10.1007/s13659-018-0193-7. Epub 2018 Nov 28.
Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC values ranging from 14.5 to 24.6 μM, with compound (1) being the most potent as compared to the positive control thiourea (IC = 21.6 μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC = 17.9 μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.
脲酶（UE）据报道是幽门螺杆菌（HP）的一种强效毒力因子，表明其与多种胃肠道疾病有关。因此，通过靶向UE可以更好地控制目前被世界卫生组织视为1类致癌物的HP的传播。正是基于此，我们合成了天然存在的齐墩果-12-烯-3-酮（1）的三种新衍生物（2-4），该化合物先前是从无花果榕（桑科）的果实中分离得到的。在合成的化合物中，3和4含有吲哚部分。它们的结构通过光谱和光谱技术（1D-NMR、2D-NMR和MS）明确确定。对起始原料和合成化合物进行了UE抑制活性筛选，结果显示具有显著活性，IC值范围为14.5至24.6 μM，与阳性对照硫脲（IC = 21.6 μM）相比，化合物（1）活性最强。在合成衍生物中，化合物4活性最强（IC = 17.9 μM），而其他化合物的活性接近对照。此外，对目标化合物2-4进行了分子对接研究，以探索它们的结合模式，用于设计更有效的UE抑制剂。
