Abstract
Cyclooxygenases (COXs) play a pivotal role in inflammation, a complex phenomenon required in human defense, but also involved in the emergence of insidious human disorders. Currently-used COX-1 inhibitors (Non-Steroidal Anti-Inflammatory Drugs-NSAIDs), as the most frequent choices for the treatment of chronic inflammatory diseases, have been identified to be associated with a variety of adverse drug reactions, especially dyspepsia, as well as peptic ulcer, which lead to diminished output. Moreover, the structural similarities of COX- 1 and -2, along with the availability of comprehensive information about the three-dimensional structure of COX- 2, co-crystallized with various inhibitors, search selective COX-2 inhibitors a formidable challenge. COX-2 inhibitors were shown to minimize the incidence of metastasis in cancer patients when administered preoperatively. Developing selective COX-2 inhibitors to tackle both cancer and chronic inflammatory illnesses has been identified as a promising research direction in recent decades. Identifying innovative scaffolds to integrate as the major component of future COX-2 inhibitors is critical in this regard. The presence of a central, α, β-unsaturated carbonyl- containing scaffold, as a characteristic structural pattern in many selective COX-2 inhibitors, along with a huge count of chalcone-based anticancer agents representing the basic idea of this review; providing a survey of the most recently published literature concerning development of chalcone analogs as novel COX-2 inhibitors until 2022 with efficient anticancer activity. A brief overview of the most recent developments concerning structure- activity relationship insights and mechanisms is also reported, helping pave the road for additional investigation.
Graphical Abstract
[http://dx.doi.org/10.3390/ijms21093233] [PMID: 32370233]
[http://dx.doi.org/10.3390/cancers6031769] [PMID: 25198391]
[http://dx.doi.org/10.1080/14786419.2021.2000980] [PMID: 34865580]
[http://dx.doi.org/10.1007/s004320000225] [PMID: 11469677]
[http://dx.doi.org/10.1161/ATVBAHA.110.207449] [PMID: 21508345]
[http://dx.doi.org/10.1016/j.critrevonc.2006.01.003] [PMID: 16531064]
[http://dx.doi.org/10.1530/rep.0.1260559] [PMID: 14611628]
[http://dx.doi.org/10.1038/sj.onc.1204183] [PMID: 11313903]
[http://dx.doi.org/10.1007/s10555-011-9303-2] [PMID: 22002714]
[http://dx.doi.org/10.1111/j.1476-5381.1983.tb10028.x] [PMID: 6360279]
[http://dx.doi.org/10.1155/2016/9847840] [PMID: 27478311]
[http://dx.doi.org/10.1016/S0002-9343(97)00203-9] [PMID: 9572314]
[http://dx.doi.org/10.1038/sj.bjp.0702897] [PMID: 10578123]
[http://dx.doi.org/10.1086/317517] [PMID: 11113025]
[http://dx.doi.org/10.1111/j.1582-4934.2008.00430.x] [PMID: 18657230]
[http://dx.doi.org/10.1172/JCI27291] [PMID: 16395396]
[http://dx.doi.org/10.1016/j.abb.2014.01.026] [PMID: 24503478]
[http://dx.doi.org/10.3389/fphar.2018.00976] [PMID: 30245627]
[http://dx.doi.org/10.1194/jlr.R800042-JLR200]
[http://dx.doi.org/10.1016/j.biopha.2016.01.024]
[http://dx.doi.org/10.1158/1940-6207.CAPR-11-0157] [PMID: 21543340]
[http://dx.doi.org/10.4292/wjgpt.v5.i1.40] [PMID: 24605250]
[http://dx.doi.org/10.3390/cancers13040594] [PMID: 33546238]
[http://dx.doi.org/10.3390/ph11040101] [PMID: 30314310]
[http://dx.doi.org/10.3390/ijms21239246] [PMID: 33287464]
[http://dx.doi.org/10.1074/jbc.M909695199] [PMID: 10781614]
[http://dx.doi.org/10.1002/path.2859] [PMID: 21404275]
[http://dx.doi.org/10.1186/1476-4598-12-86] [PMID: 23915189]
[http://dx.doi.org/10.1038/onc.2008.322] [PMID: 18794809]
[http://dx.doi.org/10.1007/978-3-642-30331-9_2] [PMID: 22893198]
[http://dx.doi.org/10.2478/jvetres-2019-0030] [PMID: 31276061]
[http://dx.doi.org/10.1186/1476-4598-2-10] [PMID: 12575899]
[http://dx.doi.org/10.3390/jox11030007] [PMID: 34206277]
[http://dx.doi.org/10.3390/cells10061487] [PMID: 34199169]
[http://dx.doi.org/10.3390/biology9120434] [PMID: 33271839]
[PMID: 24250402]
[http://dx.doi.org/10.1186/s12964-021-00799-8] [PMID: 34922574]
[PMID: 12414664]
[http://dx.doi.org/10.1038/cddis.2015.305]
[http://dx.doi.org/10.1111/j.1476-5381.2011.01383.x] [PMID: 21449912]
[http://dx.doi.org/10.1155/2007/93416] [PMID: 17389773]
[http://dx.doi.org/10.1038/nrc3214] [PMID: 22318237]
[http://dx.doi.org/10.3390/cells9051133] [PMID: 32375405]
[http://dx.doi.org/10.1155/2008/704165] [PMID: 18615184]
[http://dx.doi.org/10.1155/2010/215158] [PMID: 20339581]
[http://dx.doi.org/10.1186/s12964-020-0530-4] [PMID: 32264958]
[http://dx.doi.org/10.1038/s41467-020-18794-x] [PMID: 33037194]
[http://dx.doi.org/10.1016/j.tips.2013.03.001] [PMID: 23571046]
[http://dx.doi.org/10.7150/ijms.44439] [PMID: 32410839]
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[PMID: 10728711]
[http://dx.doi.org/10.3748/wjg.v9.i6.1144] [PMID: 12800214]
[http://dx.doi.org/10.1023/A:1026575610124] [PMID: 11191059]
[http://dx.doi.org/10.1101/gad.314617.118] [PMID: 30275043]
[http://dx.doi.org/10.3389/fcimb.2020.00425] [PMID: 32974217]
[http://dx.doi.org/10.1021/jm0613166] [PMID: 17341061]
[http://dx.doi.org/10.1093/carcin/bgr016] [PMID: 21296766]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01457] [PMID: 29251920]
[http://dx.doi.org/10.1530/JME-15-0310] [PMID: 27067638]
[http://dx.doi.org/10.1016/j.jsbmb.2015.07.018] [PMID: 26277097]
[http://dx.doi.org/10.1016/j.trci.2018.06.014]
[http://dx.doi.org/10.1111/j.1365-2567.2009.03225.x] [PMID: 20561356]
[http://dx.doi.org/10.3233/JAD-141506] [PMID: 25227314]
[http://dx.doi.org/10.3389/fnagi.2010.00019] [PMID: 20725517]
[http://dx.doi.org/10.1016/j.bcp.2020.114147] [PMID: 32653589]
[http://dx.doi.org/10.1523/JNEUROSCI.20-18-06862.2000] [PMID: 10995830]
[http://dx.doi.org/10.1155/S1110724304308065] [PMID: 15292582]
[PMID: 26207229]
[http://dx.doi.org/10.3389/fnagi.2019.00233] [PMID: 31543810]
[http://dx.doi.org/10.1186/s12974-022-02580-1] [PMID: 36058959]
[http://dx.doi.org/10.1212/WNL.0b013e3181d5a4a3] [PMID: 20308684]
[http://dx.doi.org/10.1371/journal.pone.0256602] [PMID: 34492069]
[http://dx.doi.org/10.1001/archneur.60.8.1059] [PMID: 12925360]
[http://dx.doi.org/10.1038/s41577-022-00684-6] [PMID: 35246670]
[http://dx.doi.org/10.3390/ph15070847] [PMID: 35890146]
[http://dx.doi.org/10.1517/13543776.2011.593510] [PMID: 21714592]
[http://dx.doi.org/10.1248/bpb.30.1450] [PMID: 17666802]
[http://dx.doi.org/10.3390/biom11060894] [PMID: 34208562]
[http://dx.doi.org/10.1016/j.bmc.2005.11.041] [PMID: 16356730]
[http://dx.doi.org/10.1016/j.bmc.2020.115960] [PMID: 33477020]
[http://dx.doi.org/10.1016/j.bmc.2006.06.022] [PMID: 16798002]
[http://dx.doi.org/10.1016/j.bmcl.2009.04.125] [PMID: 19447036]
[http://dx.doi.org/10.1016/j.bmc.2009.06.056] [PMID: 19596198]
[http://dx.doi.org/10.1016/j.apsb.2022.01.002] [PMID: 35755295]
[http://dx.doi.org/10.1016/j.bmcl.2020.127173] [PMID: 32278513]
[http://dx.doi.org/10.1186/1756-8722-2-38] [PMID: 19725977]
[http://dx.doi.org/10.1007/s12263-011-0210-5] [PMID: 21484163]
[http://dx.doi.org/10.3389/fphar.2020.592654] [PMID: 33536909]
[http://dx.doi.org/10.1016/j.ejmech.2012.02.007] [PMID: 22361686]
[http://dx.doi.org/10.1016/j.ejmech.2019.111954] [PMID: 31838326]
[http://dx.doi.org/10.1080/14756366.2017.1421181] [PMID: 29560733]
[http://dx.doi.org/10.3390/molecules23010048] [PMID: 29280968]
[http://dx.doi.org/10.3390/molecules21050653] [PMID: 27213317]
[http://dx.doi.org/10.1021/om300373t]
[http://dx.doi.org/10.1016/j.ejmech.2019.04.062] [PMID: 31096151]
[http://dx.doi.org/10.2174/1871520617666171003145533] [PMID: 28971779]
[http://dx.doi.org/10.2147/DDDT.S256756] [PMID: 32848361]
[http://dx.doi.org/10.1016/j.cdc.2021.100762]
[http://dx.doi.org/10.1016/j.molstruc.2021.130159]
[PMID: 35194442]
[http://dx.doi.org/10.1016/j.compbiolchem.2022.107748] [PMID: 35917597]
[http://dx.doi.org/10.1016/j.bioorg.2022.106171] [PMID: 36166898]
[http://dx.doi.org/10.3390/molecules26164899] [PMID: 34443487]
[http://dx.doi.org/10.1016/j.bioorg.2022.106036] [PMID: 35878450]
[http://dx.doi.org/10.1016/j.cdc.2021.100742]
[http://dx.doi.org/10.1002/slct.202100884]
[http://dx.doi.org/10.1016/j.bioorg.2018.10.064] [PMID: 30428415]
[http://dx.doi.org/10.3390/molecules23030616] [PMID: 29518053]
[http://dx.doi.org/10.1016/j.ejmech.2018.10.058] [PMID: 30388465]
[http://dx.doi.org/10.1080/14756366.2020.1861606] [PMID: 33349069]
[http://dx.doi.org/10.3390/ph15030280] [PMID: 35337078]
[http://dx.doi.org/10.3390/molecules27041158] [PMID: 35208952]
[http://dx.doi.org/10.2174/1573406414666180525133221] [PMID: 29804536]
[PMID: 35692149]
[http://dx.doi.org/10.3390/molecules26237177] [PMID: 34885754]
[http://dx.doi.org/10.1371/journal.pone.0222267] [PMID: 31553748]
[http://dx.doi.org/10.1182/blood.V5.2.155.155] [PMID: 15402271]