Abstract
Cancer is one of the severe diseases in which abnormal cells divide and proliferate in an uncontrolled manner without any regulation. Globally cancer is among the leading causes of death; according to a recent report of by the WHO, around 10 million people died in 2018 due to cancer. It has also been reported that by 2040, approximately 30 million new cases will be reported every year. The increase in the incidences of cancer is taking a toll on the health care system worldwide. Considerable scientific literature is available on anticancer agents but newer therapeutic strategies are still required in this field to address novel approaches to drug design and discovery to counter this problem. Imidazothiazole represents a privileged scaffold in medicinal chemistry and provides the medicinal chemist the possibility to modulate the physiochemical properties of the lead compound. In recent times, imidazothiazole scaffold is broadly explored for its anticancer activity, which acts through various mechanisms such as EGFR, B-RAF, DHFR kinase inhibition and tubulin polymerization inhibition and other molecular mechanisms of action. Due to their feasible synthetic accessibility and promising pharmacological profile, it has attracted various medicinal chemists to explore and develop imidazothiazole derivatives as potent and safe anticancer agents. In the present article, we have reviewed various potent imidazothiazole scaffold-based derivatives reported as anticancer agents, their synthetic strategies, Structure Activity Relationship (SAR), mechanism of action, and molecular docking along with their future perspective. This review will be very useful for medicinal chemists for drug design and development of imidazothiazole-based potent antiproliferative agents.
Graphical Abstract
[http://dx.doi.org/10.1016/j.ejmcr.2022.100042]
[http://dx.doi.org/10.3322/caac.21703] [PMID: 34878180]
[http://dx.doi.org/10.1002/ijc.33588] [PMID: 33818764]
[http://dx.doi.org/10.1002/ddr.21925] [PMID: 35297084]
[http://dx.doi.org/10.15537/smj.2022.43.5.20210742] [PMID: 35537737]
[http://dx.doi.org/10.34293/economics.v9i2.3727]
[http://dx.doi.org/10.3390/molecules26144213] [PMID: 34299488]
[http://dx.doi.org/10.1016/j.bmc.2020.115897] [PMID: 33316752]
[http://dx.doi.org/10.2174/0929867329666220318100019] [PMID: 35306982]
[http://dx.doi.org/10.1016/j.jiph.2020.02.002] [PMID: 32139293]
[http://dx.doi.org/10.2174/1573406417666201208121458] [PMID: 33292124]
[http://dx.doi.org/10.3390/molecules27092700] [PMID: 35566055]
[http://dx.doi.org/10.3390/molecules26133997] [PMID: 34208916]
[PMID: 11716438]
[PMID: 375604]
[http://dx.doi.org/10.1107/S160053680501264X]
[http://dx.doi.org/10.1038/2091084a0] [PMID: 5925183]
[http://dx.doi.org/10.2147/DDDT.S198950] [PMID: 31114157]
[http://dx.doi.org/10.1186/1476-4598-12-19] [PMID: 23497317]
[http://dx.doi.org/10.1038/srep00070] [PMID: 22355589]
[http://dx.doi.org/10.1074/jbc.M109.088682] [PMID: 20061378]
[http://dx.doi.org/10.1016/j.ejmech.2020.112640] [PMID: 32739648]
[http://dx.doi.org/10.5530/pj.2022.14.13]
[http://dx.doi.org/10.2174/1389557516666160321114917] [PMID: 26996617]
[http://dx.doi.org/10.1016/j.ejca.2006.11.007] [PMID: 17208435]
[http://dx.doi.org/10.1016/j.bioorg.2020.103811] [PMID: 32278207]
[http://dx.doi.org/10.2174/1568026620666200303123102] [PMID: 32124699]
[http://dx.doi.org/10.1016/j.xinn.2021.100103] [PMID: 34557754]
[http://dx.doi.org/10.1016/j.bmcl.2022.128529] [PMID: 35007724]
[http://dx.doi.org/10.3390/molecules24040682] [PMID: 30769844]
[http://dx.doi.org/10.1007/s13402-020-00499-4] [PMID: 32219702]
[http://dx.doi.org/10.1007/s10911-008-9079-3] [PMID: 18454307]
[http://dx.doi.org/10.1124/pharmrev.121.000381] [PMID: 34987087]
[http://dx.doi.org/10.3892/or.2018.6343] [PMID: 29620274]
[http://dx.doi.org/10.1038/onc.2015.185] [PMID: 26050618]
[http://dx.doi.org/10.1016/j.ejmech.2021.113674] [PMID: 34237622]
[http://dx.doi.org/10.1677/erc.1.01280] [PMID: 17259557]
[http://dx.doi.org/10.1016/j.ctrv.2014.07.004] [PMID: 25123819]
[http://dx.doi.org/10.3233/BD-2003-17105] [PMID: 15687676]
[http://dx.doi.org/10.1016/j.bioorg.2021.105151] [PMID: 34333424]
[http://dx.doi.org/10.1016/j.bcp.2004.04.024] [PMID: 15313400]
[http://dx.doi.org/10.1007/s10555-012-9365-9] [PMID: 22684368]
[http://dx.doi.org/10.2165/11640870-000000000-00000] [PMID: 23116250]
[PMID: 23251089]
[PMID: 12460918]
[http://dx.doi.org/10.1080/14756366.2020.1819260] [PMID: 32962435]
[http://dx.doi.org/10.1016/j.ejmech.2015.03.065] [PMID: 25841200]
[http://dx.doi.org/10.1016/j.bioorg.2020.103967] [PMID: 32470760]
[http://dx.doi.org/10.1016/j.bmc.2019.03.062] [PMID: 30955995]
[http://dx.doi.org/10.1016/j.bmcl.2020.127478] [PMID: 32781217]
[http://dx.doi.org/10.3390/molecules24061140] [PMID: 30909399]
[http://dx.doi.org/10.1021/cr00062a002]
[http://dx.doi.org/10.1517/13543776.15.8.967]
[http://dx.doi.org/10.1016/S0887-2333(99)00092-2] [PMID: 10699361]
[http://dx.doi.org/10.1007/s00280-003-0625-9] [PMID: 12819937]
[http://dx.doi.org/10.1021/acs.jmedchem.6b01253] [PMID: 28177228]
[http://dx.doi.org/10.1021/jm300644g] [PMID: 22734697]
[http://dx.doi.org/10.1016/j.bioorg.2018.05.025] [PMID: 29864684]
[http://dx.doi.org/10.1038/nrc1317] [PMID: 15057285]
[http://dx.doi.org/10.1016/S0955-0674(98)80082-3] [PMID: 9484591]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-2249] [PMID: 18347161]
[http://dx.doi.org/10.1016/j.ejmech.2014.09.051] [PMID: 25240869]
[http://dx.doi.org/10.1002/med.20080] [PMID: 16788980]
[http://dx.doi.org/10.1021/acs.jmedchem.0c01837] [PMID: 33788562]
[http://dx.doi.org/10.1016/j.ejmech.2020.112847] [PMID: 33022479]
[http://dx.doi.org/10.1016/j.bioorg.2018.02.005] [PMID: 29459129]
[http://dx.doi.org/10.1002/slct.201701563]
[http://dx.doi.org/10.1016/j.bioorg.2017.10.019] [PMID: 29102724]
[http://dx.doi.org/10.1016/j.bmc.2017.04.013] [PMID: 28462842]
[http://dx.doi.org/10.1016/j.ejmech.2016.09.060] [PMID: 27744185]
[http://dx.doi.org/10.1038/nrc2639] [PMID: 19461669]
[http://dx.doi.org/10.2174/1568009615666151030102250] [PMID: 26517538]
[http://dx.doi.org/10.1046/j.1440-1711.2003.t01-1-01177.x] [PMID: 12848846]
[http://dx.doi.org/10.4161/cc.8.12.8745] [PMID: 19448397]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1331] [PMID: 22068654]
[http://dx.doi.org/10.1172/JCI31178] [PMID: 17476344]
[http://dx.doi.org/10.1111/j.1600-065X.2008.00610.x] [PMID: 18364004]
[http://dx.doi.org/10.1021/acsmedchemlett.6b00391] [PMID: 28523098]
[http://dx.doi.org/10.1039/C7OB02529G] [PMID: 29177308]
[http://dx.doi.org/10.1080/13543776.2018.1441290] [PMID: 29473428]
[http://dx.doi.org/10.1016/j.bcp.2019.07.011] [PMID: 31306643]
[http://dx.doi.org/10.3390/molecules24101874] [PMID: 31096672]
[http://dx.doi.org/10.1021/ml500247w] [PMID: 25313323]
[http://dx.doi.org/10.1021/acs.jmedchem.9b01549] [PMID: 31961685]
[http://dx.doi.org/10.1016/j.bmcl.2014.10.030] [PMID: 25453802]
[http://dx.doi.org/10.1016/j.ejmech.2015.06.042] [PMID: 26141911]
[http://dx.doi.org/10.1039/D0MD00188K] [PMID: 33479622]
[http://dx.doi.org/10.1007/s00044-016-1684-x]
[http://dx.doi.org/10.1016/j.canlet.2005.06.037] [PMID: 16095812]
[http://dx.doi.org/10.1080/14656566.2020.1801637] [PMID: 32772726]
[http://dx.doi.org/10.18632/oncotarget.27489] [PMID: 32215183]
[http://dx.doi.org/10.2147/CMAR.S196568] [PMID: 32021432]
[http://dx.doi.org/10.1097/MOH.0000000000000698] [PMID: 34966123]
[http://dx.doi.org/10.1016/j.clml.2022.02.008] [PMID: 35418351]
[http://dx.doi.org/10.1080/14737140.2020.1782749] [PMID: 32552126]
[http://dx.doi.org/10.2174/1566524021666210111104428] [PMID: 33430730]
[http://dx.doi.org/10.1080/10406638.2022.2136215]
[http://dx.doi.org/10.2147/DDDT.S307113] [PMID: 34354342]
[http://dx.doi.org/10.2174/1389557520999201209213648] [PMID: 33302837]
[http://dx.doi.org/10.2174/1568026621666210527103225] [PMID: 34047259]
[http://dx.doi.org/10.1016/j.ejmech.2019.07.003] [PMID: 31288127]