Abstract
This review presents the detailed account of factors leading to cancer and design strategy for the synthesis of benzimidazole derivatives as anticancer agents. The recent survey for cancer treatment in Cancer facts and figures 2017 American Chemical Society has shown progressive development in fighting cancer. Researchers all over the world in both developed and developing countries are in a continuous effort to tackle this serious concern. Benzimidazole and its derivatives showed a broad range of biological activities due to their resemblance with naturally occurring nitrogenous base i.e. purine. The review discussed benzimidazole derivatives showing anticancer properties through a different mechanism viz. intercalation, alkylating agents, topoisomerases, DHFR enzymes, and tubulin inhibitors. Benzimidazole derivatives act through a different mechanism and the substituents reported from the earlier and recent research articles are prerequisites for the synthesis of targeted based benzimidazole derivatives as anticancer agents. The review focuses on an easy comparison of the substituent essential for potency and selectivity through SAR presented in figures. This will further provide a better outlook or fulfills the challenges faced in the development of novel benzimidazole derivatives as anticancer.
Keywords: Benzimidazole, cancer, metastasis, angiogenesis, SAR, Protein kinase inhibitors, cancer proliferation.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.033 ] [PMID: 22071256]
[http://dx.doi.org/10.1016/j.bmc.2006.06.020]
[http://dx.doi.org/10.1016/S0169-409X(97)00095-1 ] [PMID: 10837619]
[http://dx.doi.org/10.1016/j.ejmech.2011.11.006 ] [PMID: 22119132]
[http://dx.doi.org/10.1016/j.ejmech.2012.10.044 ] [PMID: 23202485]
[http://dx.doi.org/10.1016/j.ejmech.2012.03.028 ] [PMID: 22542105]
[http://dx.doi.org/10.1093/labmed/30.12.791]
[http://dx.doi.org/10.1016/j.ejmech.2010.08.063 ] [PMID: 20846760]
[http://dx.doi.org/10.1016/j.ejmech.2012.02.017 ] [PMID: 22373735]
[http://dx.doi.org/10.1016/j.ejmech.2012.06.012 ] [PMID: 22809559]
[http://dx.doi.org/10.1016/j.ejmech.2010.07.064 ] [PMID: 20728965]
[http://dx.doi.org/10.1016/j.ejmech.2013.12.061 ] [PMID: 24463645]
[http://dx.doi.org/10.1016/j.ejmech.2014.07.071 ] [PMID: 25064347]
[http://dx.doi.org/10.1016/j.ejmech.2012.04.007 ] [PMID: 22560627]
[http://dx.doi.org/10.1016/j.jmgm.2010.04.003 ] [PMID: 20493747]
[http://dx.doi.org/10.1016/j.ejmech.2012.11.032]
[http://dx.doi.org/10.1016/j.bmc.2015.04.028 ] [PMID: 25953722]
[http://dx.doi.org/10.1016/j.ejmech.2011.08.013 ] [PMID: 22014559]
[http://dx.doi.org/10.1016/j.ejmech.2010.04.015 ] [PMID: 20451307]
[http://dx.doi.org/10.1016/j.ejmech.2012.01.044 ] [PMID: 22357112]
[http://dx.doi.org/10.1021/cr900097c]
[http://dx.doi.org/10.1016/j.bmc.2015.02.036 ] [PMID: 25778766]
[http://dx.doi.org/10.1016/j.bmc.2015.01.004 ] [PMID: 25648686]
[http://dx.doi.org/10.1038/312237a0 ] [PMID: 6504138 ]
[http://dx.doi.org/10.1038/nrd3253] [PMID: 20885410]
[http://dx.doi.org/10.1038/nrc1317 ] [PMID: 15057285]
[http://dx.doi.org/10.1016/j.bmc.2018.02.045 ] [PMID: 29519603]
[http://dx.doi.org/10.1016/j.molliq.2018.01.140]
[http://dx.doi.org/10.1016/j.ejmech.2017.05.014 ] [PMID: 28525845]
[http://dx.doi.org/10.1016/j.bmc.2017.08.053 ] [PMID: 28917448]
[http://dx.doi.org/10.1016/j.ejmech.2017.09.006 ] [PMID: 28923381]
[http://dx.doi.org/10.1016/j.cclet.2017.03.025]
[http://dx.doi.org/10.1016/0960-894X(95)00532-4]
[http://dx.doi.org/10.1016/j.jorganchem.2015.10.008]
[http://dx.doi.org/10.1016/j.bmcl.2009.06.103 ] [PMID: 19616939]
[http://dx.doi.org/10.1016/j.ejmech.2010.02.022 ] [PMID: 20207049]
[http://dx.doi.org/10.1016/j.jinorgbio.2014.12.006 ] [PMID: 25528481]
[http://dx.doi.org/10.1016/S0223-5234(98)80027-5]
[http://dx.doi.org/10.1016/j.jphotobiol.2012.05.003 ] [PMID: 22695227]
[http://dx.doi.org/10.1016/j.saa.2013.11.006 ] [PMID: 24291450]
[http://dx.doi.org/10.1007/s11426-014-5087-x]
[http://dx.doi.org/10.1016/j.saa.2015.01.106 ] [PMID: 25706598]
[http://dx.doi.org/10.1021/jm070876h ] [PMID: 17935309]
[http://dx.doi.org/10.1021/jm8000423 ] [PMID: 18652444]
[http://dx.doi.org/10.1016/j.ejmech.2017.07.050 ] [PMID: 28763648]
[http://dx.doi.org/10.1016/j.bbrc.2004.03.093 ] [PMID: 15063810]
[http://dx.doi.org/10.1016/j.ejmech.2016.09.093 ] [PMID: 27744184]
[http://dx.doi.org/10.1016/j.ejmech.2008.06.018 ] [PMID: 18692939]
[http://dx.doi.org/10.1016/S0968-0896(00)00188-7 ] [PMID: 11092544]
[http://dx.doi.org/10.1016/j.bmc.2005.06.002 ] [PMID: 15993083]
[http://dx.doi.org/10.1016/S0014-827X(03)00042-9 ] [PMID: 12818688]
[http://dx.doi.org/10.1080/14756360802420831 ] [PMID: 18951286]
[http://dx.doi.org/10.1021/jm00018a024 ] [PMID: 7658451]
[http://dx.doi.org/10.1021/jm00046a028 ] [PMID: 7932571]
[http://dx.doi.org/10.1021/jm950412w ] [PMID: 8632422]
[http://dx.doi.org/10.1021/jm990210q ] [PMID: 10691689]
[http://dx.doi.org/10.1016/j.ejmech.2010.11.046 ] [PMID: 21186067]
[http://dx.doi.org/10.1016/j.ejmech.2007.11.020 ] [PMID: 18222567]
[http://dx.doi.org/10.1021/jm00051a010 ] [PMID: 7527862]
[http://dx.doi.org/10.1021/jm00114a003 ] [PMID: 1920349]
[http://dx.doi.org/10.1002/jps.2600710909 ] [PMID: 7131285]
[http://dx.doi.org/10.1016/j.bmcl.2015.11.083 ] [PMID: 26670841]
[http://dx.doi.org/10.1016/j.jphotobiol.2017.02.009 ] [PMID: 28222362]
[http://dx.doi.org/10.1016/j.bmc.2015.03.012 ] [PMID: 25792141]
[http://dx.doi.org/10.1016/j.bioorg.2018.02.005 ] [PMID: 29459129]
[http://dx.doi.org/10.1016/j.bmcl.2016.06.044 ] [PMID: 27515320]
[http://dx.doi.org/10.1016/j.bioorg.2015.09.003 ] [PMID: 26469740]
[http://dx.doi.org/10.1016/j.ejmech.2015.05.021 ] [PMID: 26070164]
[http://dx.doi.org/10.1016/j.bmc.2015.05.060 ] [PMID: 26169762]
[http://dx.doi.org/10.1016/j.ejmech.2014.09.071 ] [PMID: 25262051]
[http://dx.doi.org/10.1016/j.ejmech.2012.01.004 ] [PMID: 22361684]
[http://dx.doi.org/10.1016/j.ejmech.2013.06.057 ] [PMID: 23900004]
[http://dx.doi.org/10.1016/j.ejmech.2011.08.048 ] [PMID: 21944287]
[http://dx.doi.org/10.1007/s10549-012-2289-9]
[http://dx.doi.org/10.1023/A:1008209720526 ] [PMID: 9496384]
[http://dx.doi.org/10.3390/cancers3021513]
[http://dx.doi.org/10.1155/2013/546318]
[http://dx.doi.org/10.1016/j.bmc.2011.06.022 ] [PMID: 21724404]
[http://dx.doi.org/10.1016/j.compbiolchem.2016.02.001 ] [PMID: 26878127]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00056 ] [PMID: 27348537]
[http://dx.doi.org/10.1021/jm0611051 ] [PMID: 17676829]
[http://dx.doi.org/10.1111/j.1747-0285.2012.01407.x ] [PMID: 22564276]
[http://dx.doi.org/10.1016/j.ejmech.2011.11.002 ] [PMID: 22115617]
[http://dx.doi.org/10.1016/j.bmc.2015.12.041 ] [PMID: 26778657]
[http://dx.doi.org/10.1016/j.bmc.2008.12.071 ] [PMID: 19168362]
[http://dx.doi.org/10.1016/j.bmc.2009.08.047 ] [PMID: 19748274]
[http://dx.doi.org/10.1016/j.bmc.2012.05.038 ] [PMID: 22698781]
[http://dx.doi.org/10.1016/j.chembiol.2005.08.015 ] [PMID: 16298300]
[http://dx.doi.org/10.1016/j.bbapap.2005.07.039 ] [PMID: 16203192]
[http://dx.doi.org/10.1021/jm049854a ] [PMID: 15566294]
[http://dx.doi.org/10.1016/j.bbapap.2013.01.018 ] [PMID: 23360763]
[http://dx.doi.org/10.1016/j.ejphar.2017.12.018] [PMID: 29246854]
[http://dx.doi.org/10.1016/j.bmcl.2009.07.016 ] [PMID: 1964686674]
[http://dx.doi.org/10.1016/j.bmcl.2013.04.039 ] [PMID: 23664099]
[http://dx.doi.org/10.1016/j.ejmech.2015.02.036 ] [PMID: 25728022]
[http://dx.doi.org/10.1016/j.bmc.2010.09.020 ] [PMID: 20934346]
[http://dx.doi.org/10.1016/j.jphotochem.2015.05.025]
[http://dx.doi.org/10.1016/j.bmcl.2006.09.018 ] [PMID: 16997559]
[http://dx.doi.org/10.1016/j.bmcl.2014.11.078 ] [PMID: 25522820]
[http://dx.doi.org/10.1016/j.bmcl.2006.11.041 ] [PMID: 17187980]
[http://dx.doi.org/10.1016/j.bmcl.2009.01.086 ] [PMID: 19217287]
[http://dx.doi.org/10.1016/j.bmcl.2010.03.057 ] [PMID: 20399649]
[http://dx.doi.org/10.1016/j.bmcl.2007.04.045 ] [PMID: 17499505]
[http://dx.doi.org/10.1016/j.bmcl.2008.09.015 ] [PMID: 18819799]
[http://dx.doi.org/10.1016/j.bmcl.2008.12.028]
[http://dx.doi.org/10.1002/qua.24470]
[http://dx.doi.org/10.1016/j.bmcl.2010.06.009 ] [PMID: 20594842]
[http://dx.doi.org/10.1016/j.tetlet.2008.08.077]
[http://dx.doi.org/10.1016/j.jscs.2014.03.007]
[http://dx.doi.org/10.1016/j.bmcl.2010.03.033 ] [PMID: 20382528]
[http://dx.doi.org/10.1016/j.bmc.2010.09.017 ] [PMID: 20965737]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01657 ] [PMID: 27002243]
[http://dx.doi.org/10.1021/jm300717c ] [PMID: 22877085]
[http://dx.doi.org/10.1016/j.ejmech.2013.03.038 ] [PMID: 23644197]
[http://dx.doi.org/10.1016/j.bmcl.2011.02.108 ] [PMID: 21420298 ]
[http://dx.doi.org/10.1021/jm801050k ] [PMID: 18942827 ]
[http://dx.doi.org/10.1016/j.bmcl.2008.10.095 ] [PMID: 18996009]
[http://dx.doi.org/10.1016/j.bmcl.2010.01.124 ] [PMID: 20167489]
[http://dx.doi.org/10.1016/j.ejmech.2017.12.023 ] [PMID: 29316526]
[http://dx.doi.org/10.1016/j.bmcl.2006.03.059 ] [PMID: 16603354]
[http://dx.doi.org/10.1016/j.bmc.2013.12.029 ] [PMID: 24387981]
[http://dx.doi.org/10.1002/ardp.201500337 ] [PMID: 26616218]
[http://dx.doi.org/10.1016/j.ejmech.2014.06.060 ] [PMID: 24992072]
[http://dx.doi.org/10.1021/jm501613q ] [PMID: 25415869]
[http://dx.doi.org/10.1038/nrc1892]
[http://dx.doi.org/10.1021/ja805555a ] [PMID: 18973295 ]
[http://dx.doi.org/10.18632/oncotarget.15783 ] [PMID: 28423593 ]
[http://dx.doi.org/10.1021/jm401768t ] [PMID: 24432870 ]
[http://dx.doi.org/10.1016/j.ejmech.2017.04.068 ] [PMID: 28505536 ]
[http://dx.doi.org/10.1016/j.ejmech.2017.10.061 ] [PMID: 29133046 ]
[http://dx.doi.org/10.1016/j.arabjc.2017.02.007]
[http://dx.doi.org/10.1016/j.ejmech.2016.09.084 ] [PMID: 27721156]
[http://dx.doi.org/10.1016/j.bioorg.2017.04.005 ] [PMID: 28460359 ]
[http://dx.doi.org/10.1016/j.bmcl.2014.06.050 ] [PMID: 25001482 ]
[http://dx.doi.org/10.1016/j.jfluchem.2016.06.009]
[http://dx.doi.org/10.1016/j.jinorgbio.2016.11.006 ] [PMID: 27915178 ]
[http://dx.doi.org/10.1016/j.ejmech.2010.02.011 ] [PMID: 20356655 ]
[http://dx.doi.org/10.1016/j.ejmech.2010.03.022 ] [PMID: 20399544 ]
[http://dx.doi.org/10.1016/j.arabjc.2015.08.019]
[http://dx.doi.org/10.1016/j.bmcl.2014.08.064]
[http://dx.doi.org/10.1016/j.ejmech.2012.07.011]
[http://dx.doi.org/10.1016/j.arabjc.2013.02.001]
[http://dx.doi.org/10.1016/j.ejmech.2010.11.007]
[http://dx.doi.org/10.1016/j.ejmech.2011.03.062]
[http://dx.doi.org/10.1021/jm00001a016]
[http://dx.doi.org/10.1016/j.ejmech.2010.11.014]
[http://dx.doi.org/10.1016/j.ejmech.2011.04.061]
[http://dx.doi.org/10.1016/j.ejmech.2013.03.010]
[http://dx.doi.org/10.3390/molecules21050579]
[http://dx.doi.org/10.1016/j.ejmech.2011.11.008]
[http://dx.doi.org/10.1016/j.bmcl.2013.12.005]
[http://dx.doi.org/10.1016/j.ejmech.2012.04.027]
[http://dx.doi.org/10.1016/j.bmcl.2007.08.07]