Abstract
Sulfonamides have been in clinical use for many years, and the development of bioactive substances containing the sulfonamide subunit has grown steadily in view of their important biological properties such as antibacterial, antifungal, antiparasitic, antioxidant, and antitumour properties. This review addresses the medicinal chemistry aspects of sulfonamides; covering their discovery, the structure- activity relationship and the mechanism of action of the antibacterial sulfonamide class, as well as the physico-chemical and pharmacological properties associated with this class. It also provides an overview of the various biological activities inherent to sulfonamides, reporting research that emphasises the importance of this group in the planning and development of bioactive substances, with a special focus on potential antitumour properties. The synthesis of sulfonamides is considered to be simple and provides a diversity of derivatives from a wide variety of amines and sulfonyl chlorides. The sulfonamide group is a non-classical bioisostere of carboxyl groups, phenolic hydroxyl groups and amide groups. This review highlights that most of the bioactive substances have the sulfonamide group, or a related group such as sulfonylurea, in an orientation towards other functional groups. This structural characteristic was observed in molecules with distinct antibacterial activities, demonstrating a clear structure-activity relationship of sulfonamides. This short review sought to contextualise the discovery of classic antibacterial sulfonamides and their physico-chemical and pharmacological properties. The importance of the sulfonamide subunit in Medicinal Chemistry has been highlighted and emphasised, in order to promote its inclusion in the planning and synthesis of future drugs.
Keywords: Sulfonamide, sulphonamide, sulfas, antibacterial, bioisostere, anti-tumour, structure-activity relationship.
Graphical Abstract
[http://dx.doi.org/10.1038/aps.2011.156] [PMID: 22301862]
[http://dx.doi.org/10.1016/j.ejmech.2014.08.016] [PMID: 25113876]
[http://dx.doi.org/10.1016/j.tiv.2019.04.023] [PMID: 31022444]
[http://dx.doi.org/10.2174/157341210791936803]
[http://dx.doi.org/10.1055/s-0028-1129486]
[http://dx.doi.org/10.1021/ja01264a055]
[http://dx.doi.org/10.1021/cr950066q] [PMID: 11848856]
[http://dx.doi.org/10.1021/cen-v083n025.p102]
[http://dx.doi.org/10.1002/jps.2600570902] [PMID: 4877188]
[PMID: 13873645]
[PMID: 4304228]
[http://dx.doi.org/10.3109/14756366.2013.787422 PMID: 23627736]
[http://dx.doi.org/10.1016/j.femsle.2005.07.037] [PMID: 16112818]
[http://dx.doi.org/10.1016/j.molstruc.2014.05.066]
[http://dx.doi.org/10.1055/s-0029-1217020]
[http://dx.doi.org/10.2174/1570193X11310020005]
[http://dx.doi.org/10.1016/j.teac.2016.02.002]
[http://dx.doi.org/10.1021/ja01853a044]
[http://dx.doi.org/10.1021/ja01252a027]
[http://dx.doi.org/10.1002/qua.10597]
[http://dx.doi.org/10.1046/j.1365-2885.1997.00063.x PMID: 9280367]
[http://dx.doi.org/10.1023/A:1020877402759] [PMID: 12489682]
[http://dx.doi.org/10.1016/j.bmc.2004.07.049] [PMID: 15388166]
[http://dx.doi.org/10.1016/j.jmgm.2018.02.006] [PMID: 29549806]
[http://dx.doi.org/10.1016/j.xphs.2017.10.015] [PMID: 29045887]
[http://dx.doi.org/10.1016/S0960-894X(01)00134-2 PMID: 11327593]
[http://dx.doi.org/10.1021/jm1013693] [PMID: 21413808]
[http://dx.doi.org/10.1021/jo00121a038]
[http://dx.doi.org/10.1128/CMR.00007-10] [PMID: 20930076]
[http://dx.doi.org/10.2174/1385272822666180122153839]
[http://dx.doi.org/10.1590/S0100-40421999000100014]
[http://dx.doi.org/10.1016/j.trac.2008.10.001]
[http://dx.doi.org/10.1039/9781849731102-00210]
[http://dx.doi.org/10.1021/jm9014026] [PMID: 20170095]
[http://dx.doi.org/10.2174/092986708783497300] [PMID: 18288991]
[http://dx.doi.org/10.1021/jm020377a] [PMID: 12593661]
[http://dx.doi.org/10.1016/j.ejmech.2011.09.039] [PMID: 22000207]
[http://dx.doi.org/10.1016/j.ejmech.2011.08.034] [PMID: 21920638]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00764] [PMID: 26393416]
[PMID: 14583495]
[http://dx.doi.org/10.1016/j.bmc.2017.05.044] [PMID: 28576633]
[http://dx.doi.org/10.1016/j.ejmech.2017.07.020] [PMID: 28756264]
[http://dx.doi.org/10.1016/j.ejmech.2018.03.053] [PMID: 29674294]
[http://dx.doi.org/10.1016/j.ejmech.2018.04.016] [PMID: 29684705]
[http://dx.doi.org/10.1016/j.bioorg.2019.103262] [PMID: 31518757]
[http://dx.doi.org/10.1016/j.bioorg.2018.06.010] [PMID: 29966874]
[http://dx.doi.org/10.3390/molecules25102324] [PMID: 32429377]
[http://dx.doi.org/10.1080/14756366.2019.1697250 PMID: 31809607]
[http://dx.doi.org/10.1080/14756366.2019.1700240 PMID: 31813300]
[http://dx.doi.org/10.1016/j.ejmech.2019.112019] [PMID: 31972394]
[http://dx.doi.org/10.1080/14756366.2018.1515933 PMID: 30296852]
[http://dx.doi.org/10.1016/j.ejmech.2019.111815] [PMID: 31732252]
[http://dx.doi.org/10.1093/jnci/djp084] [PMID: 19351922]
[http://dx.doi.org/10.1021/jm2010223] [PMID: 22191557]
[http://dx.doi.org/10.1161/CIRCRESAHA.111.249540 PMID: 21737789]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2642 PMID: 30032112]
[http://dx.doi.org/10.1038/307131a0] [PMID: 6318122]
[http://dx.doi.org/10.1016/j.bmc.2018.07.042] [PMID: 30075999]
[http://dx.doi.org/10.2174/0929867033457647] [PMID: 12678681]
[http://dx.doi.org/10.2174/1871520617666171103140749 PMID: 29110622]
[http://dx.doi.org/10.1016/S0928-0987(00)00093-2 PMID: 10915959]
[http://dx.doi.org/10.1016/j.ejmech.2010.07.031] [PMID: 20708826]
[http://dx.doi.org/10.1007/s00044-014-1143-5]
[http://dx.doi.org/10.1016/j.bmc.2005.01.039] [PMID: 15755648]
[http://dx.doi.org/10.1016/j.ejmech.2004.03.002 PMID: 15236839]
[http://dx.doi.org/10.1080/14756366.2019.1705293 PMID: 31865756]
[http://dx.doi.org/10.2174/1389557043487402] [PMID: 14965291]
[http://dx.doi.org/10.1016/j.farmac.2005.01.005] [PMID: 15848205]
[http://dx.doi.org/10.1080/14756366.2019.1651313 PMID: 31392901]
[http://dx.doi.org/10.13171/mjc751912111445mh]
[http://dx.doi.org/10.1097/CRD.0b013e3181c61b52 PMID: 20010338]
[http://dx.doi.org/10.2337/diab.37.7.847] [PMID: 2454858]
[http://dx.doi.org/10.1016/S0968-0896(00)00305-9 PMID: 11354672]
[http://dx.doi.org/10.1021/jm801432r] [PMID: 19388676]
[http://dx.doi.org/10.1016/S0960-894X(01)00528-5 PMID: 11551771]
[http://dx.doi.org/10.2174/157340612804075133] [PMID: 22762161]
[http://dx.doi.org/10.1016/j.tetlet.2011.12.049]
[http://dx.doi.org/10.1021/jm00045a006] [PMID: 7932524]
[http://dx.doi.org/10.1248/cpb.58.1057] [PMID: 20686260]
[http://dx.doi.org/10.1016/j.bmcl.2006.04.011] [PMID: 16644213]