CN109288838A - β-咔啉-3-羧酸二聚体用于制备预防和治疗抗肺癌药物的应用 - Google Patents

β-咔啉-3-羧酸二聚体用于制备预防和治疗抗肺癌药物的应用 Download PDF

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CN109288838A
CN109288838A CN201811172317.8A CN201811172317A CN109288838A CN 109288838 A CN109288838 A CN 109288838A CN 201811172317 A CN201811172317 A CN 201811172317A CN 109288838 A CN109288838 A CN 109288838A
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王俊儒
李娜
谷红玲
代江坤
席亚玺
王世军
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Northwest A&F University
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Abstract

本发明涉及β‑咔啉‑3‑羧酸二聚体的新应用，具体涉及β‑咔啉‑3‑羧酸二聚体用于制备预防和治疗抗肺癌药物的应用，本发明所述β‑咔啉‑3‑羧酸二聚体的抗肺癌细胞活性显著高于抗其他癌细胞的活性。

Description

β-咔啉-3-羧酸二聚体用于制备预防和治疗抗肺癌药物的 应用
技术领域
本发明涉及β-咔啉-3-羧酸二聚体的应用，具体涉及及其在制备抗肺癌药物中的应用。
背景技术
上世纪六十年代，George意外合成一个β-咔啉二聚体之后，人们对β-咔啉二聚体的研究逐渐拉开序幕。2006年，徐安龙课题组设计合成了二聚体，并且测定了其以DNA为靶向的抗肿瘤活性。2008年，Amy M.Deveau等合成了一系列的β-咔啉二聚体，并测定了其体外抗肿瘤活性。2013年，马芹等报道了6个新型β-咔啉二聚体，并测定了其体外抗肿瘤活性。2014年，华会明课题组从骆驼蓬属Peganumharmala的种子中分离出一个具有八元环结构的β-咔啉二聚体PeganumineA，并测定了其体外抗肿瘤活性。2015年，Jeffrey D.Winkler课题组设计合成了两个1位连接的β-咔啉二聚体，并测定了其体外抗肿瘤活性。
发明内容
发明人研究意外发现一组β-咔啉-3-羧酸二聚体抗肺癌细胞的活性显著高于抗其他肿瘤细胞的活性，所述的一组β-咔啉-3-羧酸二聚体结构通式如式(I)所示：
具体化合物结构为：
特别是，化合物6f、6g、6m、6o和6p化合物的效果表现突出，请给出化合物的结构：
本发明的化合物具有显著的抗肺癌细胞活性，可用于制备预防和治疗抗肺癌药物的应用。
具体实施方式
以下通过合成β-咔啉-3-羧酸二聚体类化合物及其应用实例具体说明本发明的各个方面和特征。本领域的技术人员应该理解，这些实施例只是用于说明目的，而不限制本发明的范围。本发明的保护范围只受权利要求书的限制。在不背离权利要求书范围的条件下，本领域的技术人员可以对发明的各个方面进行各种修改和改进，这些修改和改进也属于本发明的保护范围。
另外，需要注意的是，除非特别指明，下面实施例中所用的各种材料和试剂都是本领域中常用的材料和试剂，可以通过常规的商业途径获得；所用的中间体可以通过常规的方法制备；所用方法均为本领域技术人员公知的常规方法。
实施例：
本发明所述化合物的合成可参考以下方法：
(一)相关中间体的合成可参考以下方法：
1,2,3,4-四氢β-咔啉-3-羧酸(中间目标物1)的合成：
称取L-色氨酸10g(49mmol)加入1000mL圆底烧瓶中，向其中加入约450mL水，搅拌、超声片刻，搅拌状态下逐滴加入0.1mol/L稀硫酸溶液，直至溶液变澄清，然后向其中加入11mL 37％甲醛水溶液，室温(25-30℃)反应5h。用饱和NaHCO3溶液将反应液PH调至6左右，放入冰箱过夜，抽滤、少量水洗，沉淀放入烘箱烘干，得到白色块状固体，即为中间目标物1(1,2,3,4-四氢β-咔啉-3-羧酸)，称重共7.23g，产率70％。
1,2,3,4-四氢β-咔啉-3-羧酸甲酯(中间目标物2)的合成：
称取中间目标物1(1,2,3,4-四氢β-咔啉-3-羧酸)500mg(约2.3mmol)加入到干燥的50mL圆底烧瓶中，向其中加入约20mL无水甲醇，冰浴下逐滴滴加1mL氯化亚砜，回流反应15h。反应液减压蒸馏，甲醇洗涤、减压蒸馏，所得固体加少量水溶解，饱和NaHCO3溶液调其PH至8左右，有大量白色沉淀生成，乙酸乙酯萃取4次，饱和食盐水洗2次，无水Na2SO4干燥，浓缩蒸干，所得固体用柱层析分离纯化，PE:EA＝1:1得白色结晶，即为中间目标物2(1,2,3,4-四氢β-咔啉-3-羧酸甲酯)，称重共339mg，产率63.7％。
β-咔啉-3-羧酸甲酯(中间目标物3)的合成：
称取中间目标物2(1,2,3,4-四氢β-咔啉-3-羧酸甲酯)3g(约13mmol)加入到干燥的250mL圆底烧瓶中，向其中加入约150mL二甲苯，加Pd/C(5％)做催化剂，回流反应48h，检测底物点消失，趁热过滤(出去钯碳)，滤液减压蒸馏，得到的固体用柱层析分离纯化，DCM:EA＝5:1得白色针状结晶，即为中间目标物3(β-咔啉-3-羧酸甲酯)，称重共2.45g，产率81.8％。
9-取代-β-咔啉-3-羧酸甲酯(中间目标物4A-D)的合成：
称取中间目标物3(β-咔啉-3-羧酸甲酯)300mg(1.33mmol)加入到干燥的250mL圆底烧瓶中，向其中加约10mLDMF溶解，加入65mg(2.7mmol)NaH，搅拌至无气泡加入溴化苄0.312mL(2.64mmol)，室温反应6h，点板检测底物反应完全，加入约20mL冰水淬灭反应，用乙酸乙酯萃取4次，饱和食盐水洗3次，无水Na2SO4干燥，浓缩蒸干，所得固体用柱层析分离纯化，PE:EA＝2:1得白色结晶，即为中间目标物4A(9-苄基-β-咔啉-3-羧酸甲酯)，称重共313.6mg，产率80.4％。
用相同的方法分别用邻甲基氯化苄、对甲基氯化苄、邻氟氯化苄与目标物3反应，分别得到化合物4B、4C、4D。
(二)最终化合物的合成参考方法：
化合物6a-6p:
β-咔啉-3-羧酸二聚体(6a-6p)的合成路线:
以二聚体化合物6a的合成为例：
称取4A(9-苄基-β-咔啉-3-羧酸甲酯)300mg(0.95mmol)加入50mL圆底烧瓶中，向其中加入约5mLTHF/CH3OH溶解，加入0.1mol/L NaOH溶液38mL，有大量白色沉淀出现，室温反应24h，至反应液澄清停止反应。反应液用乙酸乙酯萃取3次、二氯甲烷萃取1次，所得水相用0.1mol/L盐酸调PH至5左右，有大量淡黄色沉淀生成，过滤，所得沉淀烘干，即为目标物4(9-苄基-β-咔啉-3-羧酸)，直接加入下步反应。
称取中间目标物4(9-苄基-β-咔啉-3-羧酸)60mg(约0.2mmol)加入50mL圆底烧瓶中，加入约5mLDMF溶解，加入K2CO3 41mg(约0.3mmol)，半小时后加入1,3-二溴丙烷10μL约0.1mmol)，加热反应14h，点板检测底物消失，加入约20mL冰水淬灭反应，二氯甲烷萃取4次，饱和食盐水洗3次，无水Na2SO4干燥，浓缩蒸干，所得固体用柱层析分离纯化，DCM:EA＝5:1得白色片状固体，即为产物6a，称重共36.6mg，产率57.2％。
按照相同的方法，分别用二溴烷烃、二溴二甲苯与四个9-取代-β-咔啉-3-羧酸化合物反应，得到不同的β-咔啉-3-羧酸二聚体(6a-6p，如表1所示)。
表1
6a：
propane-1,3-diyl-bis-(9-benzyl-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体,产率：57.2％,m.p.:182-183℃.ESI-MS,m/z:645.38[M+H]+1.H-NMR(500MHz,CDCl3)δ8.82(dd,J＝11.7,0.7Hz,2H),8.17(d,J＝7.8Hz,1H),7.61(ddd,J＝8.2,7.3,1.1Hz,1H),7.46(d,J＝8.3Hz,1H),7.36(t,J＝7.5Hz,1H),7.26(d,J＝6.4Hz,3H),7.10(dd,J＝7.0,2.4Hz,2H),5.46(s,2H),4.72(t,J＝6.2Hz,2H),2.50–2.44(m,1H).13C-NMR(126MHz,CDCl3)δ165.97,141.69,137.87,137.80,135.75,132.04,129.05,129.00,128.52,128.09,126.52,122.22,121.52,120.91,117.76,110.09,62.81,47.11,28.51.
6b：
butane-1,4-diyl-bis-(9-benzyl-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体,产率：56.7％,m.p.:210-212℃.ESI-MS,m/z:659.40[M+H]+.1H-NMR(500MHz,CDCl3)δ8.89(d,J＝3.6Hz,2H),8.22(d,J＝7.8Hz,1H),7.59(t,J＝7.4Hz,1H),7.48(d,J＝8.3Hz,1H),7.35(t,J＝7.5Hz,1H),7.24(s,3H),7.15–7.10(m,2H),5.60(s,2H),4.56(s,2H),2.08(s,2H).13C-NMR(126MHz,CDCl3)δ166.10,143.16,141.86,138.03,135.84,134.33,132.12,129.06,128.74,128.10,126.58,122.23,121.67,120.96,117.71,110.16,65.10,47.32,25.71.
6c：
pentane-1,5-diyl-bis-(9-benzyl-9H-pyrido[3,4-b]indole-3-carboxylate)：
白色固体,产率：77.5％,m.p.:183-184℃.ESI-MS,m/z:673.45[M+H]+.1H-NMR(500MHz,CDCl3δ8.92–8.86(m,2H),8.21(d,J＝7.9Hz,1H),7.63–7.56(m,1H),7.48(d,J＝8.3Hz,1H),7.38–7.32(m,1H),7.26–7.25(m,3H),7.13(dd,J＝7.2,2.1Hz,2H),5.58(s,2H),4.51(t,J＝6.8Hz,2H),2.03–1.95(m,2H),1.70(dt,J＝15.5,7.7Hz,1H).13C-NMR(126MHz,CDCl3)δ166.15,141.84,138.19,138.01,135.85,132.11,129.08,129.03,128.75,128.12,126.60,122.23,121.66,120.95,117.68,110.15,65.38,47.31,28.65,22.67.
6d：
hexane-1,6-diyl-bis-(9-benzyl-9H-pyrido[3,4-b]indole-3-carboxylate)
白色粉末,产率：71％,m.p.:184-185℃.ESI-MS,m/z:687.41[M+H]+.1H-NMR(500MHz,CDCl3)δ8.89(d,J＝10.8Hz,2H),8.23(d,J＝7.8Hz,1H),7.63–7.58(m,1H),7.49(d,J＝8.3Hz,1H),7.36(t,J＝7.4Hz,1H),7.29–7.24(m,3H),7.17–7.11(m,2H),5.60(s,2H),4.48(t,J＝6.8Hz,2H),1.97–1.87(m,2H),1.60(dd,J＝8.7,5.4Hz,2H).13C-NMR(126MHz,CDCl3)δ166.20,141.82,138.18,137.99,135.85,132.10,129.07,129.04,128.73,128.11,126.59,122.23,121.63,120.95,117.68,110.16,65.58,47.29,28.85,25.87.
6e：
propane-1,3-diyl-bis-(9-(2-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：57.7％,m.p.:157-158℃.ESI-MS,m/z:673.43[M+H]+.1H-NMR(500MHz,CDCl3)δ8.77(s,1H),8.65(s,1H),8.18(d,J＝7.9Hz,1H),7.59(t,J＝7.7Hz,1H),7.36(dd,J＝18.8,8.0Hz,2H),7.26(s,1H),7.21(d,J＝7.5Hz,1H),7.16(t,J＝7.4Hz,1H),6.95(t,J＝7.5Hz,1H),6.48(d,J＝7.7Hz,1H),5.32(s,2H),4.72(t,J＝5.9Hz,2H),2.51–2.42(m,1H),2.37(s,3H).13C-NMR(126MHz,CDCl3)δ165.96,141.77,137.93,137.82,135.18,133.36,132.08,130.75,128.97,128.41,127.93,126.59,125.84,122.26,121.48,120.92,117.71,110.12,62.95,45.22,28.50,19.36.
6f：
butane-1,4-diyl-bis-(9-(2-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：44.2％,m.p.:211-213℃.ESI-MS m/z:687.40[M+H]+.1HNMR(500MHz,CDCl3)δ8.96(d,J＝0.7Hz,1H),8.82(d,J＝0.5Hz,1H),8.30(d,J＝7.8Hz,1H),7.67–7.60(m,1H),7.46–7.39(m,2H),7.31(s,1H),7.27(d,J＝7.4Hz,1H),7.22(t,J＝7.4Hz,1H),7.03(t,J＝7.4Hz,1H),6.62(d,J＝7.7Hz,1H),5.61(s,2H),4.62(s,2H),2.45(s,3H),2.14(t,J＝2.7Hz,2H).13CNMR(126MHz,CDCl3)δ166.12,141.94,138.15,137.99,135.28,133.43,132.18,130.78,129.05,128.70,127.96,126.61,125.99,122.24,121.58,120.99,117.76,110.24,65.12,45.51,25.69,19.37.
6g：
pentane-1,5-diyl-bis-(9-(2-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：37.9％,m.p.:145-146℃.ESI-MS m/z:701.57[M+H]+.1HNMR(500MHz,CDCl3)δ8.93(d,J＝0.6Hz,1H),8.80(d,J＝0.4Hz,1H),8.27(d,J＝7.8Hz,1H),7.66–7.59(m,1H),7.41(dd,J＝15.6,7.8Hz,2H),7.31(s,1H),7.27(d,J＝7.4Hz,1H),7.22(t,J＝7.4Hz,1H),7.02(t,J＝7.4Hz,1H),6.61(d,J＝7.7Hz,1H),5.57(s,2H),4.56(t,J＝6.8Hz,2H),2.45(s,3H),2.08–1.99(m,2H),1.78–1.72(m,1H).13CNMR(126MHz,CDCl3)δ166.15,141.91,138.10,138.07,135.27,133.43,132.16,130.78,129.01,128.67,127.96,126.60,125.99,122.21,121.56,120.95,117.68,110.19,65.36,45.47,28.61,22.61,19.36.
6h：
hexane-1,6-diyl-bis-(9-(2-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：32.6％,m.p.:189-190℃.ESI-MS m/z:715.55[M+H]+.1HNMR(500MHz,CDCl3)δ8.90(d,J＝0.8Hz,1H),8.77(d,J＝0.7Hz,1H),8.25(d,J＝7.8Hz,1H),7.59(ddd,J＝8.2,7.2,1.1Hz,1H),7.42–7.34(m,2H),7.26(s,1H),7.23(d,J＝7.4Hz,1H),7.18(t,J＝7.4Hz,1H),6.98(t,J＝7.4Hz,1H),6.58(d,J＝7.7Hz,1H),5.57(s,2H),4.48(t,J＝6.8Hz,2H),2.41(s,3H),1.96–1.88(m,2H).13CNMR(126MHz,CDCl3)δ166.20,141.94,138.13,135.29,133.45,132.16,130.78,129.04,128.71,127.96,126.60,126.00,122.22,121.59,120.97,117.68,110.22,65.58,45.50,28.84,25.86,19.37.
6i：
propane-1,3-diyl-bis-(9-(4-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：62％,m.p.:188-189℃.ESI-MS m/z:673.45[M+H]+.1HNMR(500MHz,CDCl3)δ8.93(s,1H),8.85(s,1H),8.21(d,J＝7.8Hz,1H),7.66(t,J＝7.6Hz,1H),7.51(d,J＝8.3Hz,1H),7.40(t,J＝7.3Hz,1H),7.31(s,1H),7.10(d,J＝8.0Hz,2H),7.04(d,J＝8.0Hz,2H),5.46(s,2H),4.77(t,J＝6.2Hz,2H),2.55–2.49(m,1H),2.31(s,3H).13CNMR(126MHz,CDCl3)δ165.51,141.86,137.94,137.73,136.95,132.55,131.69,129.69,129.23,128.78,126.54,122.27,121.38,121.02,117.83,110.23,62.94,46.99,28.42,21.05.
6j：
butane-1,4-diyl-bis-(9-(4-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：47％,m.p.:223-225℃.ESI-MS m/z:687.46[M+H]+.1HNMR(500MHz,CDCl3)δ8.90(d,J＝8.3Hz,2H),8.23(d,J＝7.8Hz,1H),7.60(t,J＝7.7Hz,1H),7.50(d,J＝8.3Hz,1H),7.37(s,1H),7.26(s,1H),7.06(q,J＝8.2Hz,4H),5.57(s,2H),4.57(s,2H),2.28(s,3H),2.10(s,2H).13CNMR(126MHz,CDCl3)δ166.14,141.80,137.99,137.89,137.83,132.77,132.15,129.70,129.01,128.66,126.59,122.21,121.58,120.89,117.77,110.22,65.12,47.10,25.67,21.05.
6k：
pentane-1,5-diyl-bis-(9-(4-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：50％,m.p.:109-111℃.ESI-MS m/z:701.67[M+H]+.1HNMR(500MHz,CDCl3)δ8.92(d,J＝10.5Hz,2H),8.24(d,J＝7.8Hz,1H),7.64(t,J＝7.7Hz,1H),7.53(d,J＝8.3Hz,1H),7.38(t,J＝7.5Hz,1H),7.31(s,1H),7.09(q,J＝8.1Hz,4H),5.57(s,2H),4.55(t,J＝6.8Hz,2H),2.32(s,3H),2.18–1.95(m,2H).13CNMR(126MHz,CDCl3)δ166.17,141.77,137.95,137.90,132.76,132.13,129.69,128.98,128.65,126.58,122.18,121.55,120.87,117.70,110.18,109.32,65.36,47.07,28.60,22.62,21.05.
6l：
hexane-1,6-diyl-bis-(9-(4-methylbenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：69％，m.p.:115-117℃.ESI-MS m/z:715.59[M+H]+.1HNMR(500MHz,CDCl3)δ8.90(d,J＝15.9Hz,2H),8.23(d,J＝7.8Hz,1H),7.63-7.57(m,1H),7.50(d,J＝8.3Hz,1H),7.38(s,1H),7.26(s,1H),7.06(q,J＝8.3Hz,4H),5.56(s,2H),4.48(t,J＝6.8Hz,2H),2.28(s,3H),1.98–1.88(m,2H),1.62–1.58(m,2H).13CNMR(126MHz,CDCl3)δ166.21,141.80,137.97,137.89,132.78,132.13,129.69,129.00,128.67,126.60,122.19,121.59,120.87,117.69,110.20,65.58,47.10,29.71,28.83,25.85,21.05.
6m：
propane-1,3-diyl-bis-(9-(2-fluorobenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：65.4％，m.p.:208-210℃.ESI-MS m/z:681.49[M+H]+.1HNMR(500MHz,CDCl3)δ8.86(s,1H),8.77(s,1H),8.14(d,J＝7.9Hz,1H),7.62(t,J＝7.7Hz,1H),7.48(d,J＝8.3Hz,1H),7.36(t,J＝7.5Hz,1H),7.28–7.20(m,2H),7.10(t,J＝9.3Hz,1H),6.93(t,J＝7.5Hz,1H),6.79(t,J＝7.6Hz,1H),5.45(s,2H),4.72(t,J＝5.8Hz,2H),2.50–2.43(m,1H),1.68(s,3H).13CNMR(126MHz,CDCl3)δ165.93,159.41,141.50,137.92,137.75,131.94,129.97,129.91,129.09,128.56,128.42,128.39,124.67,124.64,122.86,122.75,122.21,121.49,121.03,117.73,115.87,115.70,109.99,62.95,40.82,29.72,28.51.
6n：
butane-1,4-diyl-bis-(9-(2-fluorobenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
针状晶体，产率：50％，m.p.:213-215℃.ESI-MS m/z:695.69[M+H]+.1HNMR(500MHz,CDCl3)δ8.97(s,1H),8.90(s,1H),8.23(d,J＝7.8Hz,1H),7.63(t,J＝7.7Hz,1H),7.54(d,J＝8.3Hz,1H),7.38(t,J＝7.5Hz,1H),7.29–7.21(m,2H),7.15–7.07(m,1H),6.95(t,J＝7.5Hz,1H),6.86(t,J＝7.1Hz,1H),5.66(s,2H),4.58(s,2H),2.11(s,2H).13CNMR(126MHz,CDCl3)δ166.08,161.41,159.45,141.65,138.10,137.91,132.00,129.97,129.91,129.13,128.80,128.47,128.44,124.67,124.64,122.80,122.24,121.61,121.09,117.75,115.88,115.72,110.09,65.15,40.99,29.71,25.67.
6o：
pentane-1,5-diyl-bis-(9-(2-fluorobenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：67.8％，m.p.:187-188℃.ESI-MS m/z:709.39[M+H]+.1HNMR(500MHz,CDCl3)δ8.94(s,1H),8.87(s,1H),8.19(d,J＝7.8Hz,1H),7.61(t,J＝7.7Hz,1H),7.52(d,J＝8.3Hz,1H),7.35(t,J＝7.5Hz,1H),7.28–7.20(m,2H),7.15–7.06(m,1H),6.94(t,J＝7.5Hz,1H),6.84(t,J＝7.1Hz,1H),5.61(s,2H),4.52(t,J＝6.8Hz,2H),2.07–1.94(m,2H),1.71(dd,J＝9.3,6.2Hz,1H).13CNMR(126MHz,CDCl3)δ166.11,161.40,159.44,141.61,138.19,137.86,131.99,129.97,129.91,129.09,128.76,128.47,128.44,124.66,124.63,122.90,122.79,122.19,121.57,121.05,117.67,115.88,115.71,110.04,65.38,40.98,40.94,29.71,28.59,22.61.
6p：
hexane-1,6-diyl-bis-(9-(2-fluorobenzyl)-9H-pyrido[3,4-b]indole-3-carboxylate)
白色固体，产率：54.6％，m.p.:199-201℃.ESI-MS m/z:723.48[M+H]+.1HNMR(500MHz,CDCl3)δ8.96(s,1H),8.88(s,1H),8.23(d,J＝7.8Hz,1H),7.63(t,J＝7.7Hz,1H),7.53(d,J＝8.3Hz,1H),7.38(t,J＝7.5Hz,1H),7.29–7.20(m,2H),7.16–7.07(m,1H),6.95(t,J＝7.5Hz,1H),6.86(t,J＝7.5Hz,1H),5.65(s,2H),4.49(t,J＝6.8Hz,2H),2.05–1.89(m,2H),1.61(d,J＝7.0Hz,2H).13CNMR(126MHz,CDCl3)δ166.16,161.42,159.45,141.65,138.26,137.88,131.98,129.98,129.91,129.12,128.80,128.49,128.46,124.66,124.64,122.92,122.22,121.61,121.07,117.67,115.88,115.72,110.07,65.61,41.02,40.98,29.71,28.83,25.85.
二、本发明化合物的体外抗肺癌活性实验:
选用人肺癌细胞系(A549)、人胃癌细胞(SGC-7901)和人肝癌细胞(SMMC-7721)，采用MTT法进行IC50值测试，5-氟尿嘧啶(5-FU)作为阳性对照。
具体方法如下：将细胞以约1×104个/孔的密度接种于96孔板，每孔接种100μL，置CO2培养箱中培养至对数生长期。然后按预设的浓度梯度加入待测样品(6a-6p)，每一梯度6个重复。阴性对照组加入等体积的溶解样品用的溶剂(DMSO)。继续培养48h后，每孔加入10μL的MTT(5mg/mL)，然后置于37℃温育4h。小心除去上清后，每孔加入100μL的DMSO，振荡约15min溶解沉淀，随后用酶标仪检测OD值，波长490min。用以下公式求出每一样品浓度下的癌细胞抑制率：
抑制率％＝(1-样品组平均OD值/对照组平均OD值)×100％
应用GraphPad Prism软件，得到已测样品的IC50值。
表2

Claims (2)

1.β-咔啉-3-羧酸二聚体用于制备预防或/和治疗抗肺癌药物的应用，所述β-咔啉-3-羧酸二聚体的结构式为：
2.如权利要求1所述的应用，其特征在于，所述化合物结构为：
CN201811172317.8A 2018-10-09 2018-10-09 β-咔啉-3-羧酸二聚体用于制备预防和治疗抗肺癌药物的应用 Pending CN109288838A (zh)

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