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1、1基于反向找靶的天然产物活性研究摘 要利用计算机辅助药物设计（CADD）技术对 Chinese Bittersweet Alkaloid (1) and (2)、Pubesenside A、2-氟代腺苷和腺苷 的潜在靶标进行预测并对预测结果进行进一步的验证与分析。采用 Pharmmapper网络服务器进行初步预测，并结合文献进行筛选与验证，然后采用 Discovery Studio3.0（以下简称 DS3.0）对靶蛋白与 Chinese Bittersweet Alkaloid (1) and (2)、Pubesenside A、2-氟代腺苷和腺苷分子进行对接并对其相互作用进行进一步分析与讨论
2、。结果Pharmmapper筛选结果显示 Chinese Bittersweet Alkaloid (1) and (2)与表皮生长受体（Epidermal growth factor receptor以下简称 EGFR）的结合较好，Pubesenside A与血管内皮生长因子受体 2（Vascular endothelial growth factor receptor 2以下简称 VEGFR-2）的结合较好，2-氟代腺苷和腺苷与 -内酰胺酶（Beta-lactamase）的结合较好。查阅文献发现 EGFR是当前药物治疗非小细胞癌症的主要靶标，例如厄洛替尼、吉非替尼等 1；VEGFR-2 是
3、当前治疗肾癌的主要靶标，例如索拉菲尼等；Beta-lactamase 是著名抗生素-青霉素的靶标。DS3.0的对接结果也显示 Chinese Bittersweet Alkaloid (1) and (2)尤其是（2）与 EGFR具有静电作用、氢键、范德华力、PiPi 键等相互作用；Pubesenside A与 VEGFR-2之间具有静电作用、氢键、范德华力等相互作用；2-氟代腺苷和腺苷尤其是 2-氟代腺苷与 Beta-lactamase之间具有静电作用、氢键、范德华力、Pi 键等相互作用。本次实验就 Chinese Bittersweet Alkaloid (1) and (2)与厄洛替尼相
4、比较分别与 EGFR进行分子对接；Pubesenside A与索拉菲尼相比较并与 VEGFR-2进行分子对接；2-氟代腺苷和腺苷与青霉素相比较并分别与青霉素进行分子对接。并比较得出结论：Chinese Bittersweet Alkaloid (1) and (2)的潜在靶标最有可能是 EGFR。而且无论是在 Pharmmpper的筛选结果还是在 DS3.0中的对接结果来看 Chinese Bittersweet Alkaloid (2)与受体 EGFR的对接匹配度以及分子间相互作用的强度明显高于 Chinese Bittersweet Alkaloid (1)。Chinese Bitters
5、weet Alkaloid (2)可能是治疗非小细胞肺癌理想的新型化合物。有望成为现如今非小细胞肺癌靶向药物出现耐药性的替代药物，以及出现2严重不良反应时的替代药物。Pubesenside A的潜在靶标最有可能是 VEGFR-2，Pubesenside A可能是治疗肾癌的理想的新型化合物，有望成为代替索拉菲尼进行肾癌治疗。2-氟代腺苷和腺苷的潜在靶标可能是 Beta-lactamase，2-氟代腺苷和腺苷有望成为新型抗生素来代替青霉素等一些已经出现耐药性的抗生素的替代药物。关 键 词：CADD;Pharmmapper，Discovery Studio3.0，潜在靶标，对接论文类型：基础研究St
6、udy on the activity of natural products based on reverse targetingABSTRACTThe potential targets of Chinese Bittersweet Alkaloid (1) and (2), Pubesenside A, 2-fluoroadenosine and adenosine were predicted by computer-aided drug design (CADD) technique and the results were further validated and analyze
7、d. Pharmmapper network server for preliminary prediction, combined with the literature for screening and validation，The target protein was then docked with Chinese Bittersweet Alkaloid (1) and (2), Pubesenside A, 2-fluoroadenosine and adenosine molecules using Discovery Studio 3.0 (hereinafter DS3.0
8、) ，and its interaction for further analysis and discussion. Results The results of Pharmmapper screening showed that the combination of Chinese Bittersweet Alkaloid (1) and (2) with epidermal growth factor receptor (Epidermal growth factor receptor) was better. Pubesenside A and vascular endothelial
9、 growth factor receptor 2 (Vascular endothelial growth factor receptor 2 hereinafter referred to as VEGFR-2), the binding of 2-fluoroadenosine and adenosine to -lactamase is better. Access to the 3literature found that EGFR is the current drug treatment of non-small cell cancer, the main target, suc
10、h as erlotinib, gefitinib, etc. 1; VEGFR-2 is the main target for the treatment of renal cancer, such as sorafenib; Beta-lactamase is a well-known target for antibiotic-penicillin. The results of docking with DS3.0 also show that Chinese Bittersweet Alkaloid (1) and (2) especially (2) interact with
11、EGFR with electrostatic interactions, hydrogen bonds, van der Waals forces, Pi - Pi bonds; Pubesenside A and VEGFR - 2 2-fluoro-adenosine and adenosine, especially 2-fluoro-adenosine and Beta-lactamase between the electrostatic interaction, hydrogen bond, van der Waals force, Pi bond And so on. In t
12、his experiment, Chinese Bittersweet Alkaloid (1) and (2) were compared with erlotinib, respectively, and molecular adherence to EGFR; Pubesenside A compared with sorafenib and with VEGFR-2 molecular docking; 2-fluoro Adenosine and adenosine were compared with penicillin and were respectively conflue
13、nt to penicillin. And compare the conclusion that the potential target for Chinese Bittersweet Alkaloid (1) and (2) is most likely to be EGFR. And the docking match and the intermolecular interaction intensity of Chinese Bittersweet Alkaloid (2) with receptor EGFR were significantly higher than thos
14、e of Chinese Bittersweet Alkaloid (1), both in Pharmmppers screening results and in docking results in DS3.0. Chinese Bittersweet Alkaloid (2) may be the ideal new compound for the treatment of non-small cell lung cancer. Is expected to become now non-small cell lung cancer drug resistance drug-targ
15、eted alternative drugs, and the emergence of serious adverse reactions when the alternative drugs. The potential target for Pubesenside A is most likely to be VEGFR-2, and Pubesenside A may be the ideal new compound for the treatment of renal cell carcinoma and is expected to be a substitute for sor
16、afenib for renal cancer. The potential targets of 2-fluoroadenosine and adenosine may be Beta-lactamase, 2-fluoroadenosine and adenosine is expected to become a new antibiotic instead of penicillin and some other antibiotic resistance has been the alternative drug.4KEY WORDS: CADD; Pharmmapper, Discovery Studio 3.0, potential targets, dockingDissertation Type: Basic Research5目录基于反向找靶的天然产物活性研究 .
