摘要
背景:天然产物具有抗癌活性,常通过PI3K/Akt信号通路诱导癌细胞凋亡或自噬。天然产物的潜在疾病抑制剂已被报道,这表明疾病的一个有前途的抗癌目标。磷脂酰肌醇3激酶是一类相关的细胞内信号转导酶和脂质激酶调节不同的细胞过程中癌。 目的:确定在基于相似目标选定的莽草酸途径代谢产物对PI3Kγ活性分子的原因,详细的构效关系研究。 方法:在研究工作中,对γ型PI3K与渥曼青霉素是植物分子没食子酸和蛇形的抗癌潜力,类固醇代谢物的真菌非特异性共价抑制剂PI3K通过电子定量构效关系,采用对接,ADMET,从植物化学分离、核磁共振和体外活性。 结果:应用多元线性回归建立了预测QSAR模型,揭示了调控蛇纹石和GA抑制活性的关键结构性质。金属酸对PI3Kγ。该模型具有可接受的统计参数,如R2分别0.76,0.72,和Q2 0.55。结构分析是通过核磁共振研究。预测活动的研究通过对没食子酸和蛇形针对PI3Kγ体外试验评价R。 结论:确定的化学特征调节活性的酰胺,胺和仲胺基团的数量,最高占据分子轨道(HOMO)能量和价连接性指数x(订单2)。在硅片ADME和毒性风险评估是合规性评价进行药动学及生物利用度。
关键词: 磷脂酰肌醇-3激酶γ(PI3Kγ)、抗癌、构效关系、蛇纹石、没食子酸、对接,ADMET。
Current Cancer Drug Targets
Title:In-silico & In-vitro Identification of Structure-Activity Relationship Pattern of Serpentine & Gallic Acid Targeting PI3Kγ as Potential Anticancer Target
Volume: 17 Issue: 8
关键词: 磷脂酰肌醇-3激酶γ(PI3Kγ)、抗癌、构效关系、蛇纹石、没食子酸、对接,ADMET。
摘要: Background: Natural products showed anticancer activity and often induce apoptosis or autophagy in cancer cells through the PI3K/Akt/mTOR signaling pathways. The potential of natural products as PI3Ks inhibitors has been reported, which suggest PI3Ks a promising anticancer target. Phosphoinositide 3-kinase is a family of related intracellular signal transducer enzymes or lipid kinases that regulate different cellular processes involved in cancer.
Objective: To identify the molecular reason behind the similar target based activity of selected shikimate pathway metabolites on PI3Kγ, a detail structure-activity relationship study was performed.
Method: In the studied work, anticancer potential of plant molecules gallic acid and serpentine was evaluated against PI3Kγ isoform and compared with wortmannin, a steroid metabolite of the fungi and a non-specific covalent known inhibitor of PI3Ks by using in-silico QSAR, docking, ADMET, chemical isolation from plant, NMR and in-vitro activity.
Results: A predictive QSAR model was developed by applying multiple linear regression which revealed identification of key structural properties regulating the inhibitory activity of serpentine and gallic acid on PI3Kγ. The model exhibited acceptable statistical parameters such as r2 0.76, r2CV 0.72, and q2 0.55. Structural elucidation was done through NMR studies. Predicted activities were further evaluated through in-vitro testing of gallic acid and serpentine targeting PI3Kγ.
Conclusion: The identified chemical features modulating the activity were amide, amine, and secondary amine groups counts, highest occupied molecule orbital (HOMO) energy and valence connectivity index (order 2). In-silico ADME and toxicity risk assessment was done for pharmacokinetic and bioavailability compliance evaluation.
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In-silico & In-vitro Identification of Structure-Activity Relationship Pattern of Serpentine & Gallic Acid Targeting PI3Kγ as Potential Anticancer Target, Current Cancer Drug Targets 2017; 17 (8) . https://dx.doi.org/10.2174/1568009617666170330152617
DOI https://dx.doi.org/10.2174/1568009617666170330152617 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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