Nematallah Khaled A, Elmekkawy Sahar, Abdollah Maha R A, Elmazar Mohey M, Abdel-Sattar Essam, Meselhy Meselhy Ragab
Department of Pharmacognosy and Microbiology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo 11837, Egypt.
The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, BUE, Cairo 11837, Egypt.
ACS Omega. 2022 Feb 24;7(9):7945-7956. doi: 10.1021/acsomega.1c07011. eCollection 2022 Mar 8.
Natural products are considered as a good source of antifibrotic agents, but identifying and isolating bioactive molecule(s) is still challenging. Fortunately, numerous computational techniques have evolved to save time and efforts in this field. The aim of the current study was to utilize several cheminformatics software to study the chemical and biological features of the bark of cultivated in Egypt. Sirius software, with the aid of online databases, was used to process liquid chromatography-mass spectrometry (LC-MS) chemical profiling and predict precise molecular formulae, chemical classes, and structures. Accordingly, 37 compounds were tentatively identified, including 15 reported here for the first time from this species. Also, the BioTransformer tool was successfully applied for in silico virtual study of the human metabolism of these compounds, and 1960 different products were obtained through various metabolic pathways. Finally, an electronic library of the identified compounds and their metabolites were developed and docked in silico against eight different protein targets that are involved in the liver fibrosis process. The results revealed that the extract may have a potential hepatoprotective effect through several mechanisms and that the metabolites have the highest binding affinities to the relevant enzymes than their parent compounds. The extract was found to show potent cytotoxic activity against the liver cancer cell lines HEPG2 and HUH-7, and its absorption was enhanced through nanoformulation, as proved using the ex vivo everted gut sac method.
天然产物被认为是抗纤维化药物的良好来源，但鉴定和分离生物活性分子仍然具有挑战性。幸运的是，众多计算技术已经发展起来，以节省该领域的时间和精力。本研究的目的是利用几种化学信息学软件来研究埃及种植的[植物名称未给出]树皮的化学和生物学特性。Sirius软件借助在线数据库，用于处理液相色谱-质谱（LC-MS）化学图谱分析，并预测精确的分子式、化学类别和结构。据此，初步鉴定出37种化合物，其中15种是首次从该物种中报道。此外，BioTransformer工具成功应用于这些化合物在人体代谢的计算机虚拟研究，通过各种代谢途径获得了1960种不同的产物。最后，开发了鉴定出的化合物及其代谢产物的电子文库，并在计算机上与参与肝纤维化过程的八个不同蛋白质靶点进行对接。结果表明，该提取物可能通过多种机制具有潜在的肝保护作用，并且代谢产物与其母体化合物相比，对相关酶具有更高的结合亲和力。发现该提取物对肝癌细胞系HEPG2和HUH-7显示出强大的细胞毒性活性，并且如使用离体外翻肠囊法所证明的，其通过纳米制剂提高了吸收。
