具有靛紅結(jié)構(gòu)的吡唑衍生物的合成及其誘導非小細胞肺癌A549細胞凋亡的研究
發(fā)布時間：2018-10-05 10:32
【摘要】：基于藥效團拼合的設計原理,以4-羥基苯乙酮為原料,通過加成、環(huán)化、取代、肼解和縮合等多步反應構(gòu)建了兩類含有靛紅結(jié)構(gòu)的吡唑衍生物,共計12個目標產(chǎn)物,其結(jié)構(gòu)經(jīng)~~1H NMR,~(13)C NMR和HRMS確證.采用細胞計數(shù)試劑盒-8(CCK-8)法測試目標產(chǎn)物對人非小細胞肺癌細胞A549的體外抑制作用,部分化合物顯示出一定的抗增殖活性,其中N'-(3-亞氨基-6-氯吲哚-2-酮)-1-苯甲基-3-(4-甲氧基苯基)-1H-吡唑-5-甲酰肼(7e)和N'-(3-亞氨基-6-溴吲哚-2-酮)-1-苯甲基-3-(4-甲氧基苯基)-1H-吡唑-5-甲酰肼(7f)的IC_(50)值分別為30.41和29.69μmol/L.流式細胞術(shù)檢測表明,化合物7f能夠劑量依賴性地誘導A549細胞凋亡,并降低線粒體膜電位,但對細胞周期沒有影響.上述研究證明,目標產(chǎn)物7f能夠通過線粒體途徑誘導A549細胞凋亡,從而發(fā)揮抗腫瘤活性.
[Abstract]:Based on the design principle of pharmacophore assembly, two kinds of pyrazole derivatives with indirubin structure were synthesized from 4-hydroxyacetophenone by multi-step reactions such as addition, cyclization, substitution, hydrazine hydrolysis and condensation. Its structure was confirmed by 1H NMR,~ (13) C NMR and HRMS). The inhibitory effect of the target product on human non-small cell lung cancer cell line A549 in vitro was tested by cell count kit 8 (CCK-8). Some of the compounds showed certain antiproliferative activity. The IC_ (50) values of N- (3-Imino-6-chlorindole-2-one) -1-phenyl-methyl-3- (4-methoxyphenyl) -1H-pyrazolyl hydrazide (7e) and N- (3-imino-6-bromoindole -2-one) -1-phenylmethyl-3- (4-methoxyphenyl) -1H-pyrazole-5-formyl hydrazide (7f) were 30.41 渭 mol/L. and 29.69 渭 mol/L., respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells in a dose-dependent manner and decrease mitochondrial membrane potential, but had no effect on cell cycle. These results suggest that target product 7f can induce apoptosis of A549 cells through mitochondrial pathway, thus exerting antitumor activity.
【作者單位】： 遵義醫(yī)學院藥學院;成都大學四川抗菌素工業(yè)研究所;
【基金】：貴州省科技廳(Nos.[2014]7565,[2014]7557,[2015]6010) 遵義醫(yī)學院博士科研啟動基金(No.F-631);遵義醫(yī)學院大學生創(chuàng)新創(chuàng)業(yè)(Nos.[2014]5811,[2014]2918);遵義醫(yī)學院學科建設(藥物化學)資助項目 國家級大學生創(chuàng)新創(chuàng)業(yè)(No.201510661009)~~
【分類號】：O626;TQ460.1
本文編號：2253048
[Abstract]:Based on the design principle of pharmacophore assembly, two kinds of pyrazole derivatives with indirubin structure were synthesized from 4-hydroxyacetophenone by multi-step reactions such as addition, cyclization, substitution, hydrazine hydrolysis and condensation. Its structure was confirmed by 1H NMR,~ (13) C NMR and HRMS). The inhibitory effect of the target product on human non-small cell lung cancer cell line A549 in vitro was tested by cell count kit 8 (CCK-8). Some of the compounds showed certain antiproliferative activity. The IC_ (50) values of N- (3-Imino-6-chlorindole-2-one) -1-phenyl-methyl-3- (4-methoxyphenyl) -1H-pyrazolyl hydrazide (7e) and N- (3-imino-6-bromoindole -2-one) -1-phenylmethyl-3- (4-methoxyphenyl) -1H-pyrazole-5-formyl hydrazide (7f) were 30.41 渭 mol/L. and 29.69 渭 mol/L., respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells in a dose-dependent manner and decrease mitochondrial membrane potential, but had no effect on cell cycle. These results suggest that target product 7f can induce apoptosis of A549 cells through mitochondrial pathway, thus exerting antitumor activity.
【作者單位】： 遵義醫(yī)學院藥學院;成都大學四川抗菌素工業(yè)研究所;
【基金】：貴州省科技廳(Nos.[2014]7565,[2014]7557,[2015]6010) 遵義醫(yī)學院博士科研啟動基金(No.F-631);遵義醫(yī)學院大學生創(chuàng)新創(chuàng)業(yè)(Nos.[2014]5811,[2014]2918);遵義醫(yī)學院學科建設(藥物化學)資助項目 國家級大學生創(chuàng)新創(chuàng)業(yè)(No.201510661009)~~
【分類號】：O626;TQ460.1
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