Putri Chintya Permata Zahky Sukrisno, Rani Dinar Mutia, Untari Ludmilla Fitri, Kusumawardani Banun, Kurnia Anang, Keller Paul A, Nugraha Ari Satia
Drug Utilisation and Discovery Research Group, Faculty of Pharmacy, Universitas Jember, Jember, Indonesia 68121.
Department of Tropical Biology, Faculty of Biology, Gadjah Mada University, Yogyakarta 55281, Indonesia.
Adv Pharm Bull. 2024 Dec 30;14(4):938-943. doi: 10.34172/apb.43220. Epub 2024 Dec 13.
Lichens are well-known as a source of pharmacologically active compounds. This includes anticancer compounds which have biomass constraints including using traditional techniques of lichen bioprospecting. This current study reports the use of cutting-edge metabolomics and a computational approach to discover anticancer biomarkers from Indonesian lichens.
Seven lichen crude extracts were evaluated against cervical cell lines HeLa using a MTT assay and secondary metabolites were profiled and recorded via a gas chromatography-mass spectrometry (GC-MS) protocol. A multivariate analysis orthogonal partial least-squares-discriminant analysis (OPLS-DA) was employed to determine anticancer biomarker of the lichens. A structure-based computational study against the HeLa cancer cell related protein targets (BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM)) was used to determine the most potent biomarker.
The MTT assessment indicated the seven lichens possessed strong, medium and weak cytotoxicity. Multivariate analysis showed an OPLS-DA score plot with distinct separation among the strong, medium and weak cytotoxic groups. The biplot OPLS-DA and GC-MS analysis proposed 13 compounds of and 12 compounds of as anticancer biomarker candidates. Docking experiments revealed 6-amino-3,4,7-triphenylpyrido[2',3':4,5]thieno[2,3-]pyridazine from to possess the highest binding affinity against BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM) proteins with affinity energy values of -10.0, -11.6, -10.4, -12.6, respectively.
The study successfully revealed compound as the anticancer biomarker against HeLa cell cancer of in which can be further explored through and studies. Further, the metabolomic protocol established can be adapted as a tool for biomarker discoveries from other medicinal plants.
地衣作为药理活性化合物的来源广为人知。这包括抗癌化合物，其存在生物量限制，包括使用传统的地衣生物勘探技术。本研究报告了使用前沿的代谢组学和计算方法从印度尼西亚地衣中发现抗癌生物标志物。
使用MTT法对七种地衣粗提物进行宫颈癌细胞系HeLa评估，并通过气相色谱 - 质谱（GC-MS）方案对次生代谢产物进行分析和记录。采用多变量分析正交偏最小二乘判别分析（OPLS-DA）来确定地衣的抗癌生物标志物。针对HeLa癌细胞相关蛋白靶点（BCL-2（4MAN）、AKT-1（4GV1）、MCL-1（5FDO）和BRAF（5VAM））进行基于结构的计算研究，以确定最有效的生物标志物。
MTT评估表明这七种地衣具有强、中、弱细胞毒性。多变量分析显示OPLS-DA得分图在强、中、弱细胞毒性组之间有明显分离。双标图OPLS-DA和GC-MS分析提出了13种化合物和12种化合物作为抗癌生物标志物候选物。对接实验表明，来自的6-氨基-3,4,7-三苯基吡啶并[2',3':4,5]噻吩并[2,3-]哒嗪对BCL-2（4MAN）、AKT-1（4GV1）、MCL-1（5FDO）和BRAF（5VAM）蛋白具有最高结合亲和力，亲和能值分别为-10.0、-11.6、-10.4、-12.6。
该研究成功揭示化合物作为针对的HeLa细胞癌的抗癌生物标志物，可通过和研究进一步探索。此外，所建立的代谢组学方案可作为从其他药用植物中发现生物标志物的工具。
