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壳聚糖-海藻酸钠包覆的磁性四氧化三铁负载银纳米粒子用于吲唑并[2,1-b]酞嗪的合成及抗α-倒捻子素的人肺保护作用

Ag NPs on chitosan-alginate coated magnetite for synthesis of indazolo[2,1-b]phthalazines and human lung protective effects against α-Guttiferin.

机构信息

Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, No.97 Machang, Beijing 101149, China.

Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.

出版信息

Int J Biol Macromol. 2020 Dec 1;164:2974-2986. doi: 10.1016/j.ijbiomac.2020.08.183. Epub 2020 Aug 25.

DOI:10.1016/j.ijbiomac.2020.08.183
PMID:32853620
Abstract

Biocomposite nanomaterials have been evolved as the new generation catalysts and therapeutic supplement in these days. Magnetically isolation has added new features to this category. This has encouraged us to synthesize a novel Ag NP adorned chitosan-alginate dual bio-polysaccharide (two of the more versatile polysaccharides) modified core-shell magnetic nanocomposite (FeO/CS-Alg/Ag NPs). The material was meticulously characterized following different physicochemical techniques, such as, FT-IR, ICP-OES, FESEM, EDX, atomic mapping, TEM, VSM, XRD and XPS studies. The as synthesized material was catalytically explored in the one-pot multicomponent synthesis of biologically potent 2H-indazolo[2,1-b]phthalazine-trione derivatives involving a wide range of substrates. The reactions were ended up with excellent yields under solvent-free heating conditions. The catalyst recyclability, heterogeneity and leaching tests were performed to ensure its high stability and robustness. It could be reused as much as 10 times in succession with almost unchanged catalytic performances. In the lung protective part of the present research, the human lung toxicity was induced by α-Guttiferin. The cell viability of lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cell lines was measured by trypan blue assay. Caspase-3 activity was assessed by the caspase activity colorimetric assay kit and mitochondrial membrane potential of lung cells was studied by Rhodamine123 fluorescence dye. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test was used to show DNA fragmentation and apoptosis of lung cells. Also, the Rat inflammatory cytokine assay kit was used to measure the concentrations of inflammatory cytokines. The catalyst-treated cell cutlers significantly (p ≤ 0.01) reduced the DNA fragmentation, caspase-3 activity, and inflammatory cytokines concentrations, and raised the mitochondrial membrane potential and cell viability in the high concentration of α-Guttiferin-treated lung MRC-5, CCD19Lu, WI-38, and BEAS-2B cells. The best result of lung protective properties of catalyst against α-Guttiferin was seen in the high dose of catalyst i.e., 4 μg. DPPH test revealed similar antioxidant potentials for catalyst and butylated hydroxytoluene. The catalyst inhibited half of the DPPH molecules in the concentration of 171 μg/mL. According to the above results, catalyst can be administrated as a lung protective drug for the treatment of lung diseases after approving in the clinical trial studies in humans.

摘要

生物复合材料纳米材料已经发展成为新一代的催化剂和治疗补充剂。磁性隔离为这一类别增添了新的特点。这促使我们合成了一种新型的 Ag NP 修饰壳聚糖-海藻酸钠双生物多糖(两种更通用的多糖)修饰的核壳磁性纳米复合材料(FeO/CS-Alg/Ag NPs)。该材料经过不同的物理化学技术进行了细致的表征,如 FT-IR、ICP-OES、FESEM、EDX、原子映射、TEM、VSM、XRD 和 XPS 研究。在一锅多组分生物有效 2H-吲唑[2,1-b]苯并嗪-三酮衍生物的合成中,对合成的材料进行了催化探索,涉及广泛的底物。在无溶剂加热条件下,反应以优异的收率结束。进行了催化剂的可回收性、异质性和浸出测试,以确保其高稳定性和坚固性。它可以连续重复使用 10 次以上,催化性能几乎不变。在本研究的肺保护部分,α-古藤素诱导人肺毒性。通过台盼蓝测定法测量肺 MRC-5、CCD19Lu、WI-38 和 BEAS-2B 细胞系的细胞活力。通过 caspase 活性比色测定试剂盒评估 caspase-3 活性,通过 Rhodamine123 荧光染料研究肺细胞的线粒体膜电位。末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)试验用于显示肺细胞的 DNA 片段化和细胞凋亡。还使用大鼠炎症细胞因子测定试剂盒测量炎症细胞因子的浓度。催化剂处理的细胞切割器显著(p≤0.01)降低了 DNA 片段化、caspase-3 活性和炎症细胞因子浓度,并提高了高浓度α-古藤素处理的肺 MRC-5、CCD19Lu、WI-38 和 BEAS-2B 细胞中的线粒体膜电位和细胞活力。在高剂量催化剂(即 4μg)下,催化剂对α-古藤素的肺保护作用表现出最佳效果。DPPH 试验表明催化剂和丁基化羟基甲苯具有相似的抗氧化潜力。催化剂在 171μg/mL 的浓度下抑制了一半的 DPPH 分子。根据上述结果,在临床试验研究中获得人类批准后,催化剂可作为治疗肺部疾病的肺保护药物。

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