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Zhongpeng Ding Feifei Li Lianghui Xie Minqing Gu Chunlei Li Chang Liu Chao Peng Wenbao Li 《Marine drugs》2022,20(12)
Phenylahistin is a naturally occurring marine product with a diketopiperazine structure that can bind to the colchicine site of microtubulin as a possible anticancer agent. To develop more potent microtubule inhibitors, novel phenylahistin derivatives were designed and synthesized based on the co-crystal complexes of phenylahistin derivatives and microtubulin. We established a focused library of imidazole-type molecules for the introduction of different groups to the C-ring and A-ring of phenylahistin. Structure–activity relationship studies indicated that appropriate hydrocarbon substituents and unsaturated alkenyl substituents at the 1-position of the imidazole group are important for improving the activity of such compounds. In addition, this study found that propylamine groups could maintain the activity of these compounds, as exemplified by compound 16d (IC50 = 5.38 nM, NCI-H460). Compound 15p (IC50 = 1.03 nM, NCI-H460) with an allyl group exhibited potent cytotoxic activity at the nanomolar level against human lung cancer cell lines. Immunofluorescence assay indicated that compound 15p could efficiently inhibited microtubule polymerization and induced a high expression of caspase-3. 15p also displayed good pharmacokinetic characteristics in vitro. Additionally, the growth of H22 transplanted tumors was significantly inhibited in BALB/c mice when 15p alone was administered at 4 mg/kg, and the tumor inhibition rate was as much as 65%. Importantly, the continuous administration of 15p resulted in a lower toxicity than that of docetaxel (10 mg/kg) and cyclophosphamide (20 mg/kg). Overall, the novel allyl-imidazole-diketopiperazine-type derivatives could be considered safe and effective potential agents for cancer treatment. 相似文献
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Various hypotheses have been put forward to explain the pathogenesis of hemorrhoidal diseases. However, the etiology and mechanisms of hemorrhoids are far from clear, and as a consequence the present therapeutic objective is just to relieve or abolish the symptoms of hemorrhoids. In this review, the recent research advances on the pathophysiological characteristics that are closely associated with hemorrhoids are analyzed and discussed, which include constipation, high anal resting pressure, anal mucosa damage, aging of the anal cushion supporting tissue, blood and vessel alterations, obstruction of microcirculation and biochemical changes. 相似文献
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AIM: To investigate the cell cycle arrest induced by hypoxia, hypoxia inducible factor-1 and their possible mechanism in human ovarian cancer cell line SW626. METHODS: CoCl2, a chemical inducer of hypoxia and hypoxic cell culture chamber were used to induce chemical and physical hypoxia in human ovarian cancer cell line SW626. The method of ‘decoy’ was used to block the function of HIF-1α because it acts as the core sequence of the target gene as a competitor combined to the HIF-1α. The cells were divided into group A1 (normal oxygen), A2 (normal oxygen plus HIF-1α decoy), B1 (CoCl2), B2 (CoCl2 plus HIF-1α decoy), C1 (hypoxia) and C2 (hypoxia plus HIF-1α). The expression of the HIF-1α protein, mRNA and cell cycle analysis were detected by Western blotting, RT-PCR and flow cytometry (FCM). RESULTS: The expression level of HIF-1α protein in group B1 (3.75±1.31) and group C1 (3.48±1.01) was significantly higher than that in group A1 (0.97±0.31) (P<0.05). The expression levels of HIF-1α mRNA in group A1 (0.65±0.32) and group B1 (0.64±0.34) were significantly lower than that in group C1 (1.28±0.62) (P<0.05). Decoy had no effect in the expression of HIF-1α protein and mRNA level (P>0.05). FCM showed that the G0/G1 phase was markedly increased in group B1 (81.78±24.33) and group C1 (77.62±22.76) and was significantly higher than that in group A1 (49.49±18.54) (P<0.05), group B2 (61.54±20.84) was lower than that in group B1 with statistical significance (P<0.05) and group C2 (56.03±21.42) was lower than that in group C1 with statistical significance (P<0.05) , but the difference between group A1 and group A2 (51.77±16.45) had no statistical significance (P>0.05). CONCLUSION: Both CoCl2 and physical hypoxia could distinctly induce cell cycle arrest in G0/G1 phase and the expression of HIF-1α in human ovarian cancer cell line SW626. HIF-1α plays an important role in cell cycle arrest induced by hypoxia in human ovarian cancer cell line SW626. 相似文献
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我国农业生产应重视质量目标定位 总被引:3,自引:0,他引:3
农业质量目标定位从市场角度看经济行为,从我国特殊国情看则是地农业的功能要求。在主要农产品逐步向买方过渡的环境下,定位数据与质量并重的农业发展目标,是保持我国农业持续、稳定、协高发展的前提条件。 相似文献
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β—激素剂和生长激素对猪生长,胴体组成和肉质的影响 总被引:1,自引:0,他引:1
我国是世界肉类生产和消费大国,随着人民生活水平的提高,对瘦肉的需求量不断提高.由于脂肪沉积,饲料转化率低,降低了生产者的利益.因此减少脂肪的沉积,提高瘦肉产量已成为养猪生产的方向. 相似文献
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