Abstract
Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.
Keywords: DNA, RNA recognition, aryl-nucleobase conjugate, fluorescence, circular dichroism, bioimaging, cytotoxicity.
[http://dx.doi.org/10.1002/3527601783]
[http://dx.doi.org/10.3762/bjoc.10.312] [PMID: 25550761]
[http://dx.doi.org/10.1016/j.tet.2004.05.009]
[http://dx.doi.org/10.1016/S0040-4039(01)01386-7]
[http://dx.doi.org/10.1021/ja00131a003]
[http://dx.doi.org/10.1002/1097-0282(1999)52:2<65:AID-BIP1>3.0.CO;2-U] [PMID: 10898853]
[http://dx.doi.org/10.1016/j.dnarep.2003.10.002] [PMID: 14697754]
[http://dx.doi.org/10.1016/S0960-894X(00)00081-0] [PMID: 10782681]
[http://dx.doi.org/10.1016/S0040-4020(02)00345-9]
[http://dx.doi.org/10.1021/jm9901428] [PMID: 10602700]
[http://dx.doi.org/10.1016/S0960-894X(01)00310-9] [PMID: 11459646]
[http://dx.doi.org/10.1016/S0968-0896(01)00097-9] [PMID: 11425593]
[http://dx.doi.org/10.1016/S0960-894X(99)00681-2] [PMID: 10698457]
[http://dx.doi.org/10.1002/ejoc.200700207]
[http://dx.doi.org/10.1039/cc9960000379]
[http://dx.doi.org/10.1021/ja4057344] [PMID: 23919778]
[http://dx.doi.org/10.1016/j.bmc.2012.04.009] [PMID: 22560836]
[http://dx.doi.org/10.1016/j.bmc.2016.01.016] [PMID: 26777298]
[http://dx.doi.org/10.1093/carcin/21.7.1329] [PMID: 10874010]
[http://dx.doi.org/10.1021/ja00342a062]
[http://dx.doi.org/10.1111/j.1432-1033.1994.tb20059.x] [PMID: 8001552]
[http://dx.doi.org/10.1006/jmbi.1997.1552] [PMID: 9514735]
[http://dx.doi.org/10.1006/jmbi.1997.1551] [PMID: 9514734]
[http://dx.doi.org/10.1093/emboj/17.22.6437] [PMID: 9822590]
[http://dx.doi.org/10.1016/j.tet.2007.06.002]
[http://dx.doi.org/10.1016/j.bmc.2005.11.056] [PMID: 16413787]
[http://dx.doi.org/10.1016/j.tet.2009.04.084]
[http://dx.doi.org/10.1021/ja00842a029] [PMID: 1133418]
[http://dx.doi.org/10.7164/antibiotics.38.1596] [PMID: 2416727]
[http://dx.doi.org/10.1126/science.6474168] [PMID: 6474168]
[http://dx.doi.org/10.1021/jo0496805] [PMID: 15153026]
[http://dx.doi.org/10.1002/ejoc.200400548]
[http://dx.doi.org/10.1002/ejoc.200900530]
[http://dx.doi.org/10.1007/s00726-010-0764-3] [PMID: 20967559]
[http://dx.doi.org/10.1002/open.201400001] [PMID: 25478311]
[http://dx.doi.org/10.1002/anie.201511881] [PMID: 27060288]
[http://dx.doi.org/10.1021/jm901532h] [PMID: 20218622]
[http://dx.doi.org/10.1371/journal.pone.0052199] [PMID: 23300611]
[http://dx.doi.org/10.1021/jm00083a024] [PMID: 1548686]
[http://dx.doi.org/10.1021/bi00246a026] [PMID: 1868081]
[http://dx.doi.org/10.1073/pnas.86.13.4858] [PMID: 2544877]
[http://dx.doi.org/10.1002/poc.486]
(b)Tumir, L-M.; Piantanida, I.; Cindrić, I.J.; Hrenar, T.; Meić, Z.; Žinić, M. New permanently charged phenanthridinium–nucleobase conjugates. Interactions with nucleotides and polynucleotides and recognition of ds-polyAH+. J. Phys. Org. Chem., 2003, 16(12), 891-899.
[http://dx.doi.org/10.1002/poc.680]
(c)Tumir, L.M.; Piantanida, I.; Zinić, M.; Juranović Cindrić, I.; Meić, Z.; Kralj, M.; Tomić, S. Synthesis of phenanthridinium-bis-nucleobase conjugates, interactions with poly U, nucleotides and in vitro antitumour activity of mono- and bis-nucleobase conjugates. Eur. J. Med. Chem., 2006, 41(10), 1153-1166.
[http://dx.doi.org/10.1016/j.ejmech.2006.05.005] [PMID: 16793178]
(d)Tumir, L-M.; Grabar, M.; Tomić, S.; Piantanida, I. The interactions of bis-phenanthridinium–nucleobase conjugates with nucleotides: adenine-conjugate recognizes UMP in aqueous medium. Tetrahedron, 2010, 66(13), 2501-2513.
[http://dx.doi.org/10.1016/j.tet.2010.01.063]
[PMID: 2545340]
(b)Wong, P.; Lee, C.; Tannock, I.F. Reduction of intracellular pH as a strategy to enhance the pH-dependent cytotoxic effects of melphalan for human breast cancer cells. Clin. Cancer Res., 2005, 11(9), 3553-3557.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2472] [PMID: 15867259]
[http://dx.doi.org/10.1054/drup.2000.0119] [PMID: 11498364]
[http://dx.doi.org/10.1039/b202615e]
[http://dx.doi.org/10.1039/b500617a] [PMID: 15900326]
[http://dx.doi.org/10.1021/ja053609e] [PMID: 16173724]
[http://dx.doi.org/10.3762/bjoc.13.249] [PMID: 29259662]
[http://dx.doi.org/10.1039/c3mb25578f] [PMID: 23681361]
[http://dx.doi.org/10.1080/10610278.2015.1099655]
[PMID: 24061298]
[http://dx.doi.org/10.1016/j.ejmech.2010.02.017] [PMID: 20202724]
[http://dx.doi.org/10.1039/C7NJ02699D]
[http://dx.doi.org/10.1055/s-2004-829541]
[http://dx.doi.org/10.1248/cpb.44.1801]
[http://dx.doi.org/10.1002/jhet.5570330638]
[http://dx.doi.org/10.1021/jm010246u] [PMID: 11741471]
[http://dx.doi.org/10.1093/nar/20.6.1315] [PMID: 1561088]
[http://dx.doi.org/10.1002/1099-0690(200211)2002:22<3785:AID-EJOC3785>3.0.CO;2-4]
[http://dx.doi.org/10.1142/S1088424606000028]
[http://dx.doi.org/10.1016/j.bmc.2006.11.034] [PMID: 17161951]
[http://dx.doi.org/10.1039/c3ob40519b] [PMID: 23673772]
[http://dx.doi.org/10.3762/bjoc.10.225] [PMID: 25246976]
[http://dx.doi.org/10.1046/j.1365-2958.2001.02595.x] [PMID: 11555289]
[http://dx.doi.org/10.1073/pnas.0700041104] [PMID: 17360517]
[http://dx.doi.org/10.1021/jm800261u] [PMID: 18680270]
[http://dx.doi.org/10.1021/jm201266b] [PMID: 22280300]
[http://dx.doi.org/10.1039/C6RA00294C] [PMID: 29057072]
[http://dx.doi.org/10.1021/ja00068a033]
[http://dx.doi.org/10.1021/ja00088a021]
[http://dx.doi.org/10.1246/bcsj.68.2465]
[http://dx.doi.org/10.3998/ark.5550190.0007.207]
[http://dx.doi.org/10.1016/j.bmc.2006.04.048] [PMID: 16750375]
[http://dx.doi.org/10.1016/j.bmc.2006.05.049] [PMID: 16798003]
[http://dx.doi.org/10.1021/ja01128a527]
[http://dx.doi.org/10.1021/ja01133a543]
[http://dx.doi.org/10.1515/znb-1952-0701]
[http://dx.doi.org/10.1038/171121a0]
[http://dx.doi.org/10.1351/PAC-CON-12-06-14]
[http://dx.doi.org/10.1021/jo101813z] [PMID: 21090600]
[http://dx.doi.org/10.1016/j.ccr.2016.02.008]
[http://dx.doi.org/10.1016/j.tetlet.2011.01.145]
[http://dx.doi.org/10.1021/om5002809]
[http://dx.doi.org/10.1002/aoc.1500]
[http://dx.doi.org/10.1002/cplu.201600462]
[http://dx.doi.org/10.1007/978-3-642-60929-9_4]
[http://dx.doi.org/10.1016/S0378-1119(01)00350-X] [PMID: 11255003]
[http://dx.doi.org/10.1039/c0cc01312a]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2472] [PMID: 15867259]
[http://dx.doi.org/10.1039/C2CS35348B] [PMID: 23099561]
[http://dx.doi.org/10.1002/anie.201503048] [PMID: 26179051]
[http://dx.doi.org/10.1002/anie.200502925] [PMID: 16312004]
[http://dx.doi.org/10.1016/j.jorganchem.2014.11.017]
[http://dx.doi.org/10.1016/j.jorganchem.2015.07.012]
[http://dx.doi.org/10.1111/cbdd.12908] [PMID: 27860285]
[http://dx.doi.org/10.1021/om400294s]