Abstract
Numerous purine-containing compounds have undergone extensive investigation for their medical efficacy across various diseases. The swift progress in purine-based medicinal chemistry has brought to light the therapeutic capabilities of purine-derived compounds in addressing challenging medical conditions. Defined by a heterocyclic ring comprising a pyrimidine ring linked with an imidazole ring, purine exhibits a diverse array of therapeutic attributes. This review systematically addresses the multifaceted potential of purine derivatives in combating various diseases, including their roles as anticancer agents, antiviral compounds (anti-herpes, anti-HIV, and anti-influenzae), autoimmune and anti-inflammatory agents, antihyperuricemic and anti-gout solutions, antimicrobial agents, antitubercular compounds, anti-leishmanial agents, and anticonvulsants. Emphasis is placed on the remarkable progress made in developing purine-based compounds, elucidating their significant target sites.
The article provides a comprehensive exploration of developments in both natural and synthetic purines, offering insights into their role in managing a diverse range of illnesses. Additionally, the discussion delves into the structure-activity relationships and biological activities of the most promising purine molecules. The intriguing capabilities revealed by these purine-based scaffolds unequivocally position them at the forefront of drug candidate development. As such, this review holds potential significance for researchers actively involved in synthesizing purine-based drug candidates, providing a roadmap for the continued advancement of this promising field.
Graphical Abstract
[http://dx.doi.org/10.1016/j.bmcl.2007.12.023] [PMID: 18164978]
[http://dx.doi.org/10.1016/j.pharmthera.2007.07.004] [PMID: 17884172]
[http://dx.doi.org/10.1002/cbdv.200490033] [PMID: 17191854]
[PMID: 22931527]
[http://dx.doi.org/10.2174/1871520620666200225104558] [PMID: 32096753]
[http://dx.doi.org/10.2174/1871520617666171103140749] [PMID: 29110622]
[http://dx.doi.org/10.1039/C7MD00449D] [PMID: 30108720]
[http://dx.doi.org/10.1016/j.bmc.2017.11.026] [PMID: 29269253]
[http://dx.doi.org/10.1016/j.bmcl.2007.05.041] [PMID: 17540560]
[http://dx.doi.org/10.2174/138161212800672804] [PMID: 22571665]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0080] [PMID: 18790752]
[http://dx.doi.org/10.1021/jm801340z] [PMID: 19128055]
[http://dx.doi.org/10.1021/jm01241a002] [PMID: 14056444]
[http://dx.doi.org/10.1021/cr900028p] [PMID: 19476376]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0707] [PMID: 16103101]
[http://dx.doi.org/10.1038/nrc2292] [PMID: 18097462]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00797] [PMID: 27536893]
[http://dx.doi.org/10.1021/jm301365e] [PMID: 23116168]
[http://dx.doi.org/10.1002/adsc.201100370]
[http://dx.doi.org/10.1021/jo0517702] [PMID: 16292872]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1600] [PMID: 23090120]
[http://dx.doi.org/10.1016/j.bmc.2013.01.054] [PMID: 23434367]
[http://dx.doi.org/10.1016/j.ejmech.2011.05.047] [PMID: 21684047]
[http://dx.doi.org/10.1016/j.ejmech.2011.05.046] [PMID: 21645946]
[http://dx.doi.org/10.1016/j.steroids.2013.12.004] [PMID: 24378780]
[http://dx.doi.org/10.1016/j.ejmech.2012.01.022] [PMID: 22305341]
[http://dx.doi.org/10.1021/jm901240p] [PMID: 19924996]
[http://dx.doi.org/10.1021/jm300383k] [PMID: 22519297]
[http://dx.doi.org/10.7150/jca.13141] [PMID: 27390604]
[http://dx.doi.org/10.1007/s10555-016-9649-6] [PMID: 27913999]
[http://dx.doi.org/10.1016/j.ceb.2008.12.010] [PMID: 19208461]
[http://dx.doi.org/10.1038/nrc2656] [PMID: 19536107]
[http://dx.doi.org/10.3390/cancers9050052] [PMID: 28513565]
[http://dx.doi.org/10.1002/chem.201302117] [PMID: 24105896]
[http://dx.doi.org/10.1038/s41568-020-0245-2] [PMID: 32112045]
[http://dx.doi.org/10.1093/jnci/djv335] [PMID: 26553781]
[http://dx.doi.org/10.1186/s13045-018-0624-2] [PMID: 29925402]
[http://dx.doi.org/10.1080/14737140.2018.1527688] [PMID: 30259761]
[http://dx.doi.org/10.1016/j.ejmech.2018.03.062] [PMID: 29631132]
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0876] [PMID: 28576946]
[http://dx.doi.org/10.1517/13543776.2015.1089233] [PMID: 26372795]
[http://dx.doi.org/10.1016/j.ejmech.2016.02.018] [PMID: 26907156]
[http://dx.doi.org/10.1021/jm0408767] [PMID: 15689155]
[http://dx.doi.org/10.1016/j.bmc.2005.12.060] [PMID: 16503144]
[http://dx.doi.org/10.1016/j.cbpa.2010.02.018] [PMID: 20303320]
[http://dx.doi.org/10.1073/pnas.0600001103] [PMID: 16754879]
[http://dx.doi.org/10.1016/j.bmcl.2014.02.075] [PMID: 24685542]
[http://dx.doi.org/10.1002/(SICI)1097-4652(200007)184:1<1::AID-JCP1>3.0.CO;2-7] [PMID: 10825229]
[http://dx.doi.org/10.1016/j.bioorg.2016.05.005] [PMID: 27239721]
[http://dx.doi.org/10.1038/nrd2133] [PMID: 16955068]
[http://dx.doi.org/10.1016/j.jmb.2004.02.006] [PMID: 15050820]
[http://dx.doi.org/10.1016/j.canlet.2008.08.016] [PMID: 18824292]
[http://dx.doi.org/10.1038/35106079] [PMID: 11902574]
[http://dx.doi.org/10.1016/j.gene.2005.09.010] [PMID: 16289629]
[http://dx.doi.org/10.1021/jm7011408] [PMID: 18247554]
[http://dx.doi.org/10.1016/j.ejmech.2011.08.045] [PMID: 21924799]
[http://dx.doi.org/10.1021/jm0303094] [PMID: 14613312]
[http://dx.doi.org/10.2174/092986711794839188] [PMID: 21143121]
[http://dx.doi.org/10.1038/3293] [PMID: 9809555]
[http://dx.doi.org/10.1006/abbi.1999.1206] [PMID: 10328810]
[http://dx.doi.org/10.2174/156800505774912901] [PMID: 16535863]
[http://dx.doi.org/10.1006/viro.1997.8786] [PMID: 9356335]
[http://dx.doi.org/10.1111/cbdd.12520] [PMID: 25600073]
[http://dx.doi.org/10.1021/jm00053a015] [PMID: 8421277]
[http://dx.doi.org/10.1002/cmdc.201200562] [PMID: 23386468]
[http://dx.doi.org/10.1016/j.antiviral.2016.01.005] [PMID: 26802557]
[http://dx.doi.org/10.1002/ejoc.201900727]
[http://dx.doi.org/10.1515/pac-2019-1214]
[http://dx.doi.org/10.1007/s10593-021-02929-z]
[http://dx.doi.org/10.1021/jm00345a010] [PMID: 6279842]
[http://dx.doi.org/10.1016/j.rechem.2020.100067]
[PMID: 2442214]
[http://dx.doi.org/10.1016/j.ejmech.2007.05.016] [PMID: 17640774]
[http://dx.doi.org/10.1126/science.287.5456.1279] [PMID: 10678837]
[http://dx.doi.org/10.18388/abp.1996_4522] [PMID: 8790717];
b) Lou, B. Novel strategies for solid-phase construction of small-molecule combinatorial libraries. Drug Discov. Today, 2001, 6(24), 1288-1294.
[http://dx.doi.org/10.1016/S1359-6446(01)02070-0] [PMID: 11738971];
c) Davis, J.T. G-quartets 40 years later: From 5′-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed., 2004, 43(6), 668-698.
[http://dx.doi.org/10.1002/anie.200300589] [PMID: 14755695];
d) Sabat, M.; VanRens, J.C.; Clark, M.P.; Brugel, T.A.; Maier, J.; Bookland, R.G.; Laufersweiler, M.J.; Laughlin, S.K.; Golebiowski, A.; De, B.; Hsieh, L.C.; Walter, R.L.; Mekel, M.J.; Janusz, M.J. The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-α production. Bioorg. Med. Chem. Lett., 2006, 16(16), 4360-4365.
[http://dx.doi.org/10.1016/j.bmcl.2006.05.050] [PMID: 16750367]
[http://dx.doi.org/10.1038/nbt0298-190] [PMID: 9487529]
[http://dx.doi.org/10.1002/(SICI)1099-1352(199901/02)12:1<67::AID-JMR443>3.0.CO;2-4] [PMID: 10398398]
[http://dx.doi.org/10.1016/S0165-022X(01)00212-3] [PMID: 11694293];
b) Fassina, G.; Verdoliva, A.; Odierna, M.R.; Ruvo, M.; Cassini, G. Protein a mimetic peptide ligand for affinity purification of antibodies. J. Mol. Recognit., 1996, 9(5-6), 564-569.
[http://dx.doi.org/10.1002/(SICI)1099-1352(199634/12)9:5/6<564::AID-JMR302>3.0.CO;2-F] [PMID: 9174941]
[http://dx.doi.org/10.1021/bc034063t] [PMID: 13129401]
[http://dx.doi.org/10.1016/j.pain.2011.06.017] [PMID: 21764514]
[http://dx.doi.org/10.18773/austprescr.2018.022] [PMID: 29921999]
[http://dx.doi.org/10.1016/j.bioorg.2019.103015] [PMID: 31158576]
[http://dx.doi.org/10.2174/09298673113209990107] [PMID: 23409716]
[http://dx.doi.org/10.1007/s00210-015-1088-3] [PMID: 25640188]
[http://dx.doi.org/10.3389/fphar.2018.01048] [PMID: 30386231]
[http://dx.doi.org/10.1016/j.ejmech.2018.01.068] [PMID: 29407965]
[http://dx.doi.org/10.1016/j.ejmech.2018.09.021]
[http://dx.doi.org/10.1007/s00018-011-0757-8] [PMID: 21744067]
[http://dx.doi.org/10.1016/S1359-6101(02)00019-9] [PMID: 12220546]
[http://dx.doi.org/10.1186/1465-9921-10-39]
[http://dx.doi.org/10.1159/000368800] [PMID: 25532037]
[http://dx.doi.org/10.1016/j.ejphar.2005.12.059] [PMID: 16458289]
[http://dx.doi.org/10.1007/978-94-007-4549-0_8] [PMID: 22836619]
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.03.011] [PMID: 23582662]
[http://dx.doi.org/10.1021/jm501090m] [PMID: 25264825]
[http://dx.doi.org/10.1016/j.jmb.2004.01.040] [PMID: 15003452]
[http://dx.doi.org/10.1124/pr.58.1.6] [PMID: 16507884]
[http://dx.doi.org/10.1096/fasebj.9.11.7649415] [PMID: 7649415]
[http://dx.doi.org/10.1111/j.1755-5922.2011.00277.x] [PMID: 22099531]
[http://dx.doi.org/10.1002/jhet.5570220303]
[http://dx.doi.org/10.1007/s11426-017-9169-4]
[http://dx.doi.org/10.1021/acsmedchemlett.7b00514] [PMID: 29541368];
b) Zhang, Y.; Tangadanchu, V.K.R.; Bheemanaboina, R.R.Y.; Cheng, Y.; Zhou, C.H. Novel carbazole-triazole conjugates as DNA-targeting membrane active potentiators against clinical isolated fungi. Eur. J. Med. Chem., 2018, 155, 579-589.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.022] [PMID: 29913383]
[http://dx.doi.org/10.1007/s11426-015-0351-0]
[http://dx.doi.org/10.1016/j.ejmech.2019.06.093] [PMID: 31284082]
[http://dx.doi.org/10.1038/nature17042] [PMID: 26791724];
b) Levin-Reisman, I.; Ronin, I.; Gefen, O.; Braniss, I.; Shoresh, N.; Balaban, N.Q. Antibiotic tolerance facilitates the evolution of resistance. Science, 2017, 355(6327), 826-830.
[http://dx.doi.org/10.1126/science.aaj2191] [PMID: 28183996]
[http://dx.doi.org/10.1128/CMR.00030-10] [PMID: 21233508]
[http://dx.doi.org/10.1021/ja305644e] [PMID: 22803960];
b) Lin, S.; Koh, J.J.; Aung, T.T.; Sin, W.L.W.; Lim, F.; Wang, L.; Lakshminarayanan, R.; Zhou, L.; Tan, D.T.H.; Cao, D.; Beuerman, R.W.; Ren, L.; Liu, S. Semisynthetic flavone-derived antimicrobials with therapeutic potential against methicillin-resistant Staphylococcus aureus (MRSA). J. Med. Chem., 2017, 60(14), 6152-6165.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00380] [PMID: 28636355]
[http://dx.doi.org/10.1038/nmicrobiol.2017.28] [PMID: 28263303]
[http://dx.doi.org/10.2174/15680266113139990125] [PMID: 23895097]
[http://dx.doi.org/10.1016/j.ejmech.2016.08.029] [PMID: 27614408];
b) Liu, H.B.; Gao, W.W.; Tangadanchu, V.K.R.; Zhou, C.H.; Geng, R.X. Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2018, 143, 66-84.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.027] [PMID: 29172083]
[http://dx.doi.org/10.1016/j.bmcl.2018.03.046] [PMID: 29598912]
[http://dx.doi.org/10.1128/JB.187.23.8020-8025.2005] [PMID: 16291675]
[http://dx.doi.org/10.1016/S0021-9258(17)31657-5] [PMID: 8083238]
[http://dx.doi.org/10.1016/j.bmc.2007.07.034] [PMID: 17804243]
[http://dx.doi.org/10.1021/jm0408924] [PMID: 15801862]
[http://dx.doi.org/10.1021/ja211042r] [PMID: 22188377]
[http://dx.doi.org/10.1126/science.1171583] [PMID: 19299584]
[http://dx.doi.org/10.1002/emmm.201303575] [PMID: 24500695]
[http://dx.doi.org/10.1021/jm401382v] [PMID: 24215368]
[http://dx.doi.org/10.1128/AAC.02020-19] [PMID: 32229496]
[http://dx.doi.org/10.1016/S0166-6851(01)00220-1] [PMID: 11295173]
[http://dx.doi.org/10.1016/S0166-6851(97)00218-1] [PMID: 9580532]
[http://dx.doi.org/10.1074/jbc.M300813200] [PMID: 12682070]
[http://dx.doi.org/10.1016/j.bbapap.2005.08.018] [PMID: 16198642]
[http://dx.doi.org/10.1016/S0960-894X(03)00632-2] [PMID: 12941319]
[http://dx.doi.org/10.2174/156802607780636726] [PMID: 17504130]
[http://dx.doi.org/10.1016/j.eplepsyres.2009.10.007] [PMID: 19926254]
[PMID: 12892539]
[http://dx.doi.org/10.2165/00023210-200822090-00003] [PMID: 18698874]
[http://dx.doi.org/10.1111/j.1528-1167.2009.02234.x] [PMID: 19702732]
[http://dx.doi.org/10.1111/j.1747-0285.2009.00776.x] [PMID: 19207467]
[http://dx.doi.org/10.1016/j.ejmech.2008.07.010] [PMID: 18752871]
[http://dx.doi.org/10.1248/cpb.58.326] [PMID: 20190436]
[http://dx.doi.org/10.1016/j.ejmech.2010.03.041] [PMID: 20416982]