Abstract
Cancer is the leading cause of death and the most significant determinant of life expectancy in almost every country in this twenty-first century. According to the World Health Organization (WHO), cancer is responsible for the leading cause of death globally. Benzophenone derivatives are found in a variety of naturally occurring compounds which are known to be pharmacologically efficacious against a variety of diseases, including cancer. Microtubules are thought to be a good target for cancer chemotherapies. Microtubule polymerization and depolymerization are induced by a variety of natural, synthetic, and semisynthetic chemicals having a benzophenone nucleus, affecting tubulin dynamics. Several medications that affect microtubule dynamics are in various stages of clinical trials, including Combretastatins (phase II), Vincristine (clinically approved), Paclitaxel (in clinical usage), and epothilone (phase III), and only a few have been patented. Benzophenone derivatives target the colchicine binding site of microtubules, damage them and cause cell cycle arrest in the G2-M phase. Belonging to this class of molecules, phenstatin, a potent inhibitor of tubulin polymerization, has shown strongly inhibit cancer cell growth and arrest the G2/M phase of the cell cycle by targeting the colchicine binding site of microtubules. In the present manuscript, we described the benzophenone as tubulin polymerization inhibitors, their Structure-Activity Relationships (SARs) and molecular docking studies that reveal its binding affinity with the colchicine binding site.
Keywords: Microtubule targeting agents, SAR, G2-M phase, benzophenone analogues, colchicine binding site, tubulin polymerization inhibitor, molecular docking.
[PMID: 28244479]
[http://dx.doi.org/10.3390/cancers11091375] [PMID: 31527531]
[http://dx.doi.org/10.1353/pbm.2019.0046] [PMID: 31761807]
[http://dx.doi.org/10.1158/1055-9965.EPI-15-0578] [PMID: 26667886]
[http://dx.doi.org/10.1016/j.jcrpr.2017.07.001]
[http://dx.doi.org/10.3390/ijms19040970] [PMID: 29570697]
[http://dx.doi.org/10.1155/S1110724302001985] [PMID: 12488582]
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[http://dx.doi.org/10.1186/s13044-020-00091-w] [PMID: 33292371]
[http://dx.doi.org/10.1016/j.ctrv.2006.01.006] [PMID: 16524666]
[http://dx.doi.org/10.1016/j.ejpb.2015.03.018] [PMID: 25813885]
[http://dx.doi.org/10.1016/S0092-8674(02)00625-6] [PMID: 11832206]
[http://dx.doi.org/10.1039/C9RA08192E]
[http://dx.doi.org/10.1016/S0960-894X(02)00850-8] [PMID: 12467626]
[http://dx.doi.org/10.2147/DDDT.S321824] [PMID: 34408404]
[http://dx.doi.org/10.1016/j.bioorg.2004.04.003] [PMID: 15210336]
[http://dx.doi.org/10.1128/AAC.49.10.4046-4051.2005] [PMID: 16189079]
[http://dx.doi.org/10.1021/jm900519b] [PMID: 19653650]
[http://dx.doi.org/10.4103/0250-474X.102542] [PMID: 23204621]
[http://dx.doi.org/10.1016/j.bmc.2021.116597] [PMID: 34995858]
[http://dx.doi.org/10.1128/EC.00225-14] [PMID: 25380753]
[http://dx.doi.org/10.3390/cells9102146] [PMID: 32977446]
[http://dx.doi.org/10.1016/j.bbabio.2006.04.013] [PMID: 16729962]
[http://dx.doi.org/10.1016/j.pbiomolbio.2019.10.004] [PMID: 31678255]
[http://dx.doi.org/10.1016/j.ejmech.2014.09.051] [PMID: 25240869]
[http://dx.doi.org/10.1038/s41580-021-00399-x] [PMID: 34408299]
[http://dx.doi.org/10.1002/(SICI)1098-1128(199807)18:4<259:AID-MED3>3.0.CO;2-U] [PMID: 9664292]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0791] [PMID: 24435445]
[http://dx.doi.org/10.3390/cancers13225650] [PMID: 34830812]
[http://dx.doi.org/10.1073/pnas.1408124111] [PMID: 25114240]
[http://dx.doi.org/10.1039/C7RA12173C]
[http://dx.doi.org/10.1016/j.ejmech.2017.11.062] [PMID: 29223097]
[http://dx.doi.org/10.1038/nrm2369] [PMID: 18322465]
[http://dx.doi.org/10.1016/j.pharmthera.2020.107552] [PMID: 32305312]
[http://dx.doi.org/10.1016/j.chembiol.2013.01.014] [PMID: 23521789]
[http://dx.doi.org/10.1146/annurev.cellbio.16.1.89] [PMID: 11031231]
[http://dx.doi.org/10.4161/cbt.9.10.11453] [PMID: 20234172]
[http://dx.doi.org/10.1016/j.bmc.2014.02.036] [PMID: 24680057]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0577] [PMID: 29180476]
[http://dx.doi.org/10.1007/s11095-012-0828-z] [PMID: 22814904]
[http://dx.doi.org/10.1016/j.ejmech.2018.04.011] [PMID: 29649743]
[http://dx.doi.org/10.3390/molecules21111468] [PMID: 27827858]
[http://dx.doi.org/10.1016/S1572-5995(08)80025-7]
[http://dx.doi.org/10.1039/C4OB00978A] [PMID: 25198908]
[http://dx.doi.org/10.1002/cmdc.201000479] [PMID: 21360819]
[http://dx.doi.org/10.1007/s00044-013-0582-8]
[http://dx.doi.org/10.1016/j.bmc.2012.05.059] [PMID: 22727370]
[http://dx.doi.org/10.1016/j.bmcl.2014.03.076] [PMID: 24736114]
[http://dx.doi.org/10.1021/jm010365+] [PMID: 12036364]
[http://dx.doi.org/10.1021/jm0305974] [PMID: 15139768]
[http://dx.doi.org/10.1080/00397911.2010.521435]
[http://dx.doi.org/10.1021/ml5001883] [PMID: 25313318]
[http://dx.doi.org/10.1016/j.ejmech.2016.03.040]
[http://dx.doi.org/10.1016/j.bioorg.2017.01.011] [PMID: 28139247]
[http://dx.doi.org/10.1002/ardp.201300298] [PMID: 24170414]
[http://dx.doi.org/10.1016/j.ejmech.2014.02.061] [PMID: 24657567]
[http://dx.doi.org/10.2174/157018010791526250]
[http://dx.doi.org/10.1016/j.bioorg.2020.104265] [PMID: 32919128]
[http://dx.doi.org/10.1248/cpb.45.1470] [PMID: 9331999]