Abstract
Introduction: Cancer is reported to be one of the most life-threatening diseases. Major limitations of currently used anticancer agents are drug resistance, very small therapeutic index, and severe, multiple side effects.
Objective: The current scenario necessitates developing new anticancer agents, acting on novel targets for effectively controlling cancer. The epidermal growth factor receptor is one such target, which is being explored for 1,3,4-oxadiazole and chalcone nuclei.
Methods: Findings of different researchers working on these scaffolds have been reviewed and analyzed, and the outcomes were summarized. This review focuses on Structure-Activity Relationship studies (SARs) and computational studies of various 1,3,4-oxadiazole and chalcone hybrids/ derivatives reported as cytotoxic/EGFR-TK inhibitory anticancer activity.
Result and Conclusion: 1,3,4-oxadiazole and chalcone hybrids/derivatives with varied substitutions are found to be effective pharmacophores in obtaining potent anticancer activity. Having done a thorough literature survey, we conclude that this review will surely provide firm and better insights to the researchers to design and develop potent hybrids/derivatives that inhibit EGFR.
Keywords: 1, 3, 4-oxadiazole, chalcone, hybrids, cytotoxic anticancer activity, EGFR-TK inhibitors, cancer.
Graphical Abstract
[http://dx.doi.org/10.2174/1389557516666160321114917 ] [PMID: 26996617]
[http://dx.doi.org/10.1021/bi00379a035 ] [PMID: 3494473]
[http://dx.doi.org/10.1038/311483a0 ] [PMID: 6090945]
[http://dx.doi.org/10.1016/j.bioorg.2020.103811 ] [PMID: 32278207]
[http://dx.doi.org/10.1038/msb4100014] [PMID: 16729045]
[http://dx.doi.org/10.4046/trd.2016.79.4.248 ] [PMID: 27790276]
[http://dx.doi.org/10.1177/1758834010370698 ] [PMID: 21789142]
[http://dx.doi.org/10.2174/156800912799277430 ] [PMID: 22229252]
[http://dx.doi.org/10.2174/13816128113196660764 ] [PMID: 24138713]
[http://dx.doi.org/10.1016/j.ejmech.2017.05.027 ] [PMID: 28526474]
[http://dx.doi.org/10.1016/j.bmc.2019.02.012 ] [PMID: 30744932]
[http://dx.doi.org/10.1183/09059180.00005110 ] [PMID: 20956191]
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.100 ] [PMID: 23953842]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01310 ] [PMID: 29136465]
[http://dx.doi.org/10.1016/j.bmcl.2016.02.067 ] [PMID: 26968253]
[http://dx.doi.org/10.2174/0929867323666160510123604 ] [PMID: 27160532]
[http://dx.doi.org/10.1159/000447578 ] [PMID: 27462979]
[http://dx.doi.org/10.3389/fonc.2020.00904 ] [PMID: 32714857]
[http://dx.doi.org/10.1016/j.ejmech.2020.112995 ] [PMID: 33243531]
[http://dx.doi.org/10.1016/j.bioorg.2019.102997 ] [PMID: 31136902]
[http://dx.doi.org/10.1016/j.bmcl.2020.127327 ] [PMID: 32631532]
[http://dx.doi.org/10.1016/j.ejmech.2017.07.033 ] [PMID: 28760313]
[http://dx.doi.org/10.1016/j.ejmech.2016.08.039]
[http://dx.doi.org/10.2174/1574887111666160330120431 ] [PMID: 27028971]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00840 ] [PMID: 26882288]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01310 ] [PMID: 29136465]
[http://dx.doi.org/10.1007/s10555-017-9687-8 ] [PMID: 28866730]
[http://dx.doi.org/10.1002/ardp.201600063 ] [PMID: 27258393]
[http://dx.doi.org/10.4155/fmc-2016-0222 ] [PMID: 28504890]
[http://dx.doi.org/10.2174/1389450111314070009 ] [PMID: 23547755]
[http://dx.doi.org/10.2174/1568026619666181129144107 ] [PMID: 30499396]
[http://dx.doi.org/10.1016/j.phrs.2018.11.014 ] [PMID: 30500458]
[http://dx.doi.org/10.1016/j.ejmech.2014.01.018 ] [PMID: 24607998]
[http://dx.doi.org/10.1016/j.jsps.2016.06.005 ] [PMID: 28344479]
[http://dx.doi.org/10.1016/j.compbiolchem.2016.02.001 ] [PMID: 26878127]
[http://dx.doi.org/10.1016/j.molstruc.2019.127487]
[PMID: 30502626]
[http://dx.doi.org/10.1016/j.ejmech.2019.111700 ] [PMID: 31546197]
[http://dx.doi.org/10.1016/j.bmcl.2018.10.016 ] [PMID: 30337229]
[http://dx.doi.org/10.1039/C5OB00842E ] [PMID: 26346902]
[http://dx.doi.org/10.1016/j.bmcl.2018.05.020 ] [PMID: 29789259]
[http://dx.doi.org/10.1016/j.ejmech.2016.04.035 ] [PMID: 27155466]
[http://dx.doi.org/10.1016/j.bioorg.2021.104873 ] [PMID: 33845381]
[http://dx.doi.org/10.2174/138955712801264800 ] [PMID: 22512560]
[http://dx.doi.org/10.1021/acs.chemrev.7b00020 ] [PMID: 28488435]
[http://dx.doi.org/10.2174/2213337206666190306155140]
[http://dx.doi.org/10.2174/1389557518666181015152433 ] [PMID: 30324877]
[http://dx.doi.org/10.1080/00397911.2017.1360911]
[http://dx.doi.org/10.1016/j.ejmech.2015.04.051 ] [PMID: 25965776]
[http://dx.doi.org/10.1016/j.bmc.2005.09.053 ] [PMID: 16242340]
[http://dx.doi.org/10.1016/j.jsps.2011.03.002 ] [PMID: 23960753]
[http://dx.doi.org/10.1007/s00044-010-9455-6]
[http://dx.doi.org/10.1016/j.ejmech.2012.03.056 ] [PMID: 22542958]
[http://dx.doi.org/10.1016/j.ejmech.2011.12.013 ] [PMID: 22204901]
[http://dx.doi.org/10.1016/j.ejmech.2012.04.027 ] [PMID: 22608854]
[http://dx.doi.org/10.1016/j.arabjc.2014.01.015]
[http://dx.doi.org/10.1248/bpb.b14-00867 ] [PMID: 25947922]
[http://dx.doi.org/10.1016/j.ejmech.2016.12.014 ] [PMID: 27987485]
[http://dx.doi.org/10.1016/j.ejmech.2019.111693 ] [PMID: 31539778]
[http://dx.doi.org/10.1016/j.bionut.2014.04.003]
[http://dx.doi.org/10.1016/S0167-4838(01)00276-X ] [PMID: 11755203]
[http://dx.doi.org/10.1016/j.ejmech.2011.07.016 ] [PMID: 21816517]
[http://dx.doi.org/10.1016/j.ejmech.2013.04.064 ] [PMID: 23771043]
[http://dx.doi.org/10.3390/ijms19092552 ] [PMID: 30154363]
[http://dx.doi.org/10.1016/j.bmcl.2017.08.038 ] [PMID: 28838690]
[http://dx.doi.org/10.1007/s00044-013-0791-1]