Abstract
Objective: We reported herein the synthesis of novel arylazo derivatives 3a-e incorporating isoquinoline moiety.
Methods: A coupling reaction of 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 1 with diazotized heterocyclic amines 2 in ethanol in the presence of sodium acetate to give arylazo derivatives 3a-e.
Results: Cytotoxic effect of five arylazo derivatives on breast carcinoma MCF7 and hepatocellular carcinoma HepG2 was carried out, followed by molecular and functional-based assays, to estimate the anticancer effect of these compounds. The fibroblast growth factor receptor (FGFR) and epithelial growth factor receptor (EGFR) were found to interact and bind with the compounds 3a and 3d through several hydrophobic and hydrogen bonds, which were validated by molecular docking.
Conclusion: The two promising compounds 3a and 3d demonstrated various anticancer potential activities on tumorigenesis, cytotoxicity, and apoptotic effects, exhibited in the deregulation of the expression of different genes involved in apoptotic and anti-apoptotic mechanisms, cell cycle arrest at G2/M, and induction of apoptosis in both cell lines.
Graphical Abstract
[http://dx.doi.org/10.1081/SCC-120002405]
[http://dx.doi.org/10.1016/j.ejmech.2010.09.026] [PMID: 20933305]
[http://dx.doi.org/10.1016/j.bmc.2009.10.012] [PMID: 19864149]
[http://dx.doi.org/10.1016/j.cplett.2004.07.057]
[http://dx.doi.org/10.3998/ark.5550190.0009.h28]
[http://dx.doi.org/10.1021/jm00274a035] [PMID: 5019571]
[http://dx.doi.org/10.1007/s00253-007-1302-4] [PMID: 18084755]
[http://dx.doi.org/10.1016/j.enzmictec.2006.12.005]
[http://dx.doi.org/10.1007/BF03246164]
[http://dx.doi.org/10.1016/0040-4020(96)00024-5]
[http://dx.doi.org/10.1515/znb-2011-0313]
[http://dx.doi.org/10.2174/187152062219220930154651] [PMID: 36221179]
[http://dx.doi.org/10.2174/1871520622666220429134818] [PMID: 36221180]
[http://dx.doi.org/10.1002/1522-2675(20010516)84:5<1172:AID-HLCA1172>3.0.CO;2-X]
[http://dx.doi.org/10.1080/10426500210218]
[http://dx.doi.org/10.1515/znb-2007-0116]
[http://dx.doi.org/10.3987/COM-09-11648]
[http://dx.doi.org/10.3987/COM-12-12572]
[http://dx.doi.org/10.5560/znb.2013-3101]
[http://dx.doi.org/10.1002/jhet.2891]
[http://dx.doi.org/10.4236/ns.2011.38089]
[http://dx.doi.org/10.1007/s10637-020-00987-2] [PMID: 32856275]
[http://dx.doi.org/10.2174/1871520619666191024121116] [PMID: 31696811]
[http://dx.doi.org/10.2174/1389557520666200130104632] [PMID: 32000650]
[http://dx.doi.org/10.1016/j.tetlet.2019.151265]
[http://dx.doi.org/10.1055/s-0039-1690902]
[http://dx.doi.org/10.1002/jhet.3565]
[http://dx.doi.org/10.3987/COM-21-14494]
[http://dx.doi.org/10.3987/COM-21-14579]
[http://dx.doi.org/10.1016/j.bioorg.2017.05.012] [PMID: 28601699]
[http://dx.doi.org/10.1016/j.bioorg.2017.01.009] [PMID: 28143658]
[http://dx.doi.org/10.1016/j.ejmech.2017.11.045] [PMID: 29207336]
[http://dx.doi.org/10.1093/nar/gkab294] [PMID: 33950214]
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.12.021] [PMID: 31870798]