Jayaprakash Prajisha, Begum Twahira, Lal Mohan
Agro-Technology and Rural Development Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam India.
In Silico Pharmacol. 2024 Dec 24;13(1):3. doi: 10.1007/s40203-024-00289-y. eCollection 2025.
A network pharmacology approach was used to construct comprehensive pharmacological networks, elucidating the interactions between agarwood compounds and key biological targets associated with cancer pathways. We have employed a combination of network pharmacology, molecular docking and molecular dynamics to unravel agarwood plants' active components and potential mechanisms. Reported 23 molecules were collected from the agarwood plants and considered to identify molecular targets. Further, we identified ten potent targets related to cancer through network pharmacology analysis. The key targets include EGFR, JUN, TP53, SRC, MAPK3, ACTB, GAPDH, AKT1, MYC and CTNNB1. The biological processes include the negative regulation of fibroblast proliferation, metabolic, oxidative, and more. Subsequently, molecular docking results have indicated that 7-isopropenyl-1, 4a-dimethyl-4, 4a, 5,6,7,8-hexahydro-3 H-naphthalen-2-one showed an excellent binding affinity for all ten targets. This is the first study; we employed a novel integrated approach that combines network pharmacology, molecular docking and molecular dynamics simulation (MDS). The GO and KEGG, pathway enrichment analyses, shed light on biological processes relevant to cancer treatment. Moreover, molecular docking studies results indicated that the molecule 7-isopropenyl-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one exhibited strong binding affinity among all ten cancer targets, with a docking score ranging from - 9.9 to - 6.7 kcal/mol and found to have hydrogen bond interaction with Lys168, Ser322, Thr336 and Ala946 residues. MDS sheds light on the stability of their binding, the longevity of their interactions, and their overall effect on the enzyme's active site throughout the simulation. The current work signifies the initial report using bioinformatics approaches to assess the anticancer properties of compounds derived from the agarwood plant.
采用网络药理学方法构建综合药理学网络，阐明沉香化合物与癌症通路相关关键生物学靶点之间的相互作用。我们结合网络药理学、分子对接和分子动力学来揭示沉香植物的活性成分和潜在机制。从沉香植物中收集了报道的23种分子，并考虑用于鉴定分子靶点。此外，通过网络药理学分析，我们确定了10个与癌症相关的潜在靶点。关键靶点包括表皮生长因子受体（EGFR）、原癌基因蛋白（JUN）、肿瘤蛋白p53（TP53）、原癌基因酪氨酸蛋白激酶（SRC）、丝裂原活化蛋白激酶3（MAPK3）、肌动蛋白（ACTB）、甘油醛-3-磷酸脱氢酶（GAPDH）、蛋白激酶B1（AKT1）、原癌基因蛋白（MYC）和β-连环蛋白1（CTNNB1）。生物学过程包括对成纤维细胞增殖的负调控、代谢、氧化等。随后，分子对接结果表明，7-异丙烯基-1,4a-二甲基-4,4a,5,6,7,8-六氢-3H-萘-2-酮对所有10个靶点均表现出优异的结合亲和力。这是第一项研究；我们采用了一种新颖的综合方法，将网络药理学、分子对接和分子动力学模拟（MDS）相结合。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析揭示了与癌症治疗相关的生物学过程。此外，分子对接研究结果表明，分子7-异丙烯基-1,4a-二甲基-4,4a,5,6,7,8-六氢-3H-萘-2-酮在所有10个癌症靶点中均表现出较强的结合亲和力，对接分数范围为-9.9至-6.7千卡/摩尔，并发现与赖氨酸168、丝氨酸322、苏氨酸336和丙氨酸946残基存在氢键相互作用。分子动力学模拟揭示了它们结合的稳定性、相互作用的持续时间以及在整个模拟过程中它们对酶活性位点的总体影响。目前的工作标志着首次使用生物信息学方法评估沉香植物衍生化合物的抗癌特性。
