摘要
在世界范围内,抗糖尿病药物的使用在不断增加,并且治疗方法的发展也非常广泛。仍然,当前可用的抗糖尿病药仍不具有期望的功效,并且通常与严重的不良反应有关。因此,需要全新的干预措施来解决2型糖尿病的潜在病因。查耳酮,陆生植物的次生代谢产物和类黄酮生物合成的前体已在传统医学中长期使用 广泛的生物活性,其中抗糖尿病活性突出。 这篇综述系统化了文献中有关查耳酮在体外和体内的抗糖尿病特性的信息。查尔酮可以通过在不同的治疗靶标中发挥作用来发挥这些特性:二肽基肽酶4(DPP-4); 4型葡萄糖转运蛋白(GLUT4),葡萄糖共转运蛋白2(SGLT2),α-淀粉酶,α-葡萄糖苷酶,醛糖还原酶(ALR),蛋白酪氨酸磷酸酶1B(PTP1B),过氧化物酶体增殖物激活受体-γ(PPARγ)和腺苷一磷酸(AMP)激活的蛋白激酶(AMPK)。毫无疑问,查耳酮是有前途的抗糖尿病药,并且已经建立了一些关键的结构特征。从结构-活性关系分析中,通常可以说,其骨架中羟基,异戊二烯基和香叶基的存在提高了其对所评估的抗糖尿病靶标的活性。
关键词: 抗糖尿病药物,查耳酮,二肽基肽酶4(DPP-4),4型葡萄糖转运蛋白(GLUT4), 葡萄糖钠转运蛋白2(SGLT2),α-淀粉酶,α-葡萄糖苷酶,醛糖还原酶(ALR),蛋白酪氨酸 磷酸酶1B(PTP1B),过氧化物酶体增殖物激活的受体-γ(PPARγ),单磷酸腺苷 (AMP)激活的蛋白激酶(AMPK),结构-活性关系(SAR)。
[http://dx.doi.org/10.1021/acs.chemrev.7b00020] [PMID: 28488435]
[http://dx.doi.org/10.1007/s11164-017-2977-5]
[http://dx.doi.org/10.2174/157488410790410579] [PMID: 19891604]
[http://dx.doi.org/10.1016/j.ejmech.2006.09.019] [PMID: 17112640]
[http://dx.doi.org/10.2174/1871520615666150101130800] [PMID: 25553434]
[http://dx.doi.org/10.3390/molecules22081210] [PMID: 28757583]
[http://dx.doi.org/10.2174/1385272819666141013224253]
[http://dx.doi.org/10.1007/s11101-014-9387-8]
[http://dx.doi.org/10.1016/j.bmc.2015.12.024] [PMID: 26762836]
[http://dx.doi.org/10.1517/13543776.2014.995627] [PMID: 25598152]
[http://dx.doi.org/10.1155/2013/815621] [PMID: 23690855]
[http://dx.doi.org/10.1016/S2221-1691(12)60067-7] [PMID: 23569941]
[http://dx.doi.org/10.1016/j.jsps.2015.03.013] [PMID: 27752226]
[http://dx.doi.org/10.4172/2155-6156.1000541]
[http://dx.doi.org/10.2337/dc17-S005] [PMID: 27979889]
[http://dx.doi.org/10.1007/s40273-015-0268-9] [PMID: 25787932]
[http://dx.doi.org/10.1002/psb.1500]
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[http://dx.doi.org/10.1111/j.2040-1124.2010.00022.x] [PMID: 24843404]
[http://dx.doi.org/10.1016/j.pbiomolbio.2011.07.010] [PMID: 21820006]
[http://dx.doi.org/10.4103/2230-8210.176351] [PMID: 27042424]
[http://dx.doi.org/10.2147/DDDT.S37647] [PMID: 24068868]
[http://dx.doi.org/10.4172/2167-065X.1000117]
[http://dx.doi.org/10.2174/1871522216666160216225721]
[http://dx.doi.org/10.1016/j.metabol.2014.06.018] [PMID: 25104103]
[http://dx.doi.org/10.1021/acs.jmedchem.6b01134] [PMID: 28098449]
[http://dx.doi.org/10.1111/dom.13003] [PMID: 28477418]
[http://dx.doi.org/10.1002/dmrr.2403] [PMID: 23463735]
[http://dx.doi.org/10.2337/dc17-S009]
[http://dx.doi.org/10.1016/j.cmet.2007.03.006] [PMID: 17403369]
[http://dx.doi.org/10.1016/j.mam.2012.07.001] [PMID: 23506862]
[http://dx.doi.org/10.1016/j.bbrc.2016.10.056] [PMID: 27769857]
[http://dx.doi.org/10.1007/s00580-014-1967-x]
[http://dx.doi.org/10.1093/jn/138.4.685] [PMID: 18356321]
[http://dx.doi.org/10.3346/jkms.2014.29.1.90] [PMID: 24431911]
[PMID: 24864650]
[http://dx.doi.org/10.1517/14656566.2015.1070827] [PMID: 26255950]
[http://dx.doi.org/10.1007/s00018-007-6514-3] [PMID: 17497245]
[http://dx.doi.org/10.3389/fphar.2012.00087] [PMID: 22582044]
[http://dx.doi.org/10.1002/14651858.CD004572.pub2] [PMID: 17943821]
[http://dx.doi.org/10.2337/dc05-2370] [PMID: 16801576]
[http://dx.doi.org/10.1016/j.fct.2017.11.039] [PMID: 29175190]
[http://dx.doi.org/10.1016/S1534-5807(02)00148-X] [PMID: 11970898]
[http://dx.doi.org/10.1517/13543776.2014.947268] [PMID: 25120222]
[http://dx.doi.org/10.2174/157339907779802067] [PMID: 18220654]
[http://dx.doi.org/10.1016/j.dsx.2014.09.015] [PMID: 25450819]
[http://dx.doi.org/10.1016/j.cmet.2014.08.005] [PMID: 25242225]
[http://dx.doi.org/10.1111/dom.12101] [PMID: 23522285]
[http://dx.doi.org/10.2147/DMSO.S43731] [PMID: 25018645]
[http://dx.doi.org/10.1038/emm.2016.16] [PMID: 27034026]
[http://dx.doi.org/10.2337/dc17-S011]
[http://dx.doi.org/10.5483/BMBRep.2011.44.6.410] [PMID: 21699755]
[http://dx.doi.org/10.1007/s11418-015-0914-8] [PMID: 25921859]
[http://dx.doi.org/10.1016/j.bmcl.2004.07.082] [PMID: 15380212]
[http://dx.doi.org/10.1007/s11745-016-4154-9] [PMID: 27098252]
[http://dx.doi.org/10.1016/j.nutres.2015.05.010] [PMID: 26077869]
[http://dx.doi.org/10.1002/mnfr.201000267] [PMID: 20938990]
[http://dx.doi.org/10.1002/ptr.3416] [PMID: 21305634]
[http://dx.doi.org/10.1021/acs.jafc.6b05445] [PMID: 28132506]
[http://dx.doi.org/10.1016/j.bmcl.2005.08.087] [PMID: 16202584]
[http://dx.doi.org/10.1021/jf303078r] [PMID: 23013379]
[http://dx.doi.org/10.1007/s11033-010-0271-3] [PMID: 20857221]
[http://dx.doi.org/10.1248/bpb.29.302] [PMID: 16462036]
[http://dx.doi.org/10.1016/j.fitote.2012.07.005] [PMID: 22814126]
[http://dx.doi.org/10.1016/j.ejmech.2014.04.018] [PMID: 24780600]
[http://dx.doi.org/10.1016/j.ejmech.2017.02.007] [PMID: 28242551]
[http://dx.doi.org/10.1002/cbdv.200590029] [PMID: 17191997]
[http://dx.doi.org/10.1016/j.ejmech.2015.10.017] [PMID: 26491979]
[http://dx.doi.org/10.1021/jf500426z] [PMID: 24897556]
[http://dx.doi.org/10.1016/j.bmcl.2015.08.059] [PMID: 26351039]
[http://dx.doi.org/10.1021/jf903068k] [PMID: 19954213]
[http://dx.doi.org/10.1111/cbdd.12666] [PMID: 26362113]
[http://dx.doi.org/10.1016/j.ijbiomac.2016.11.089] [PMID: 27894824]
[http://dx.doi.org/10.3390/molecules22111862] [PMID: 29084164]
[http://dx.doi.org/10.1055/s-2006-960950] [PMID: 2118267]
[http://dx.doi.org/10.1210/jcem.74.2.1370506] [PMID: 1370506]
[http://dx.doi.org/10.1248/cpb.48.1786] [PMID: 11086916]
[http://dx.doi.org/10.1211/0022357011775983] [PMID: 11370705]
[http://dx.doi.org/10.1211/jpp.60.9.0016] [PMID: 18718128]
[http://dx.doi.org/10.1248/bpb.31.1626] [PMID: 18670102]
[http://dx.doi.org/10.1016/S0223-5234(99)80010-5]
[http://dx.doi.org/10.1021/np0601861] [PMID: 17125223]
[http://dx.doi.org/10.1111/j.1747-0285.2012.01431.x] [PMID: 22805439]
[http://dx.doi.org/10.1055/s-0034-1368400] [PMID: 24782228]
[http://dx.doi.org/10.1016/j.bmcl.2015.04.003] [PMID: 25891102]
[http://dx.doi.org/10.1007/s13659-015-0082-2] [PMID: 26791751]
[http://dx.doi.org/10.1691/ph.2014.3824] [PMID: 24791588]
[http://dx.doi.org/10.1016/j.bmcl.2011.04.057] [PMID: 21555221]
[http://dx.doi.org/10.1016/j.bmcl.2009.07.054] [PMID: 19632832]
[http://dx.doi.org/10.1021/np060477+] [PMID: 17489632]
[http://dx.doi.org/10.1021/jm900964r] [PMID: 19807106]
[http://dx.doi.org/10.1248/cpb.54.368] [PMID: 16508194]
[http://dx.doi.org/10.1016/j.jnutbio.2011.03.021] [PMID: 21840191]
[http://dx.doi.org/10.1021/jf070720q] [PMID: 17583349]
[http://dx.doi.org/10.1016/j.phymed.2016.05.004] [PMID: 27387397]
[http://dx.doi.org/10.1016/j.metabol.2015.12.010] [PMID: 26975545]
[http://dx.doi.org/10.1016/j.bmcl.2013.04.027] [PMID: 23639538]
[http://dx.doi.org/10.1016/0952-3278(91)90022-W] [PMID: 1840007]
[http://dx.doi.org/10.18388/abp.2010_2443] [PMID: 21060897]
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