Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study

Abstract

A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b-9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b-9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC range of 7.7-14.2 µg/ml, in comparison with the reference drugs 5-fluorouracil (IC = 7.9 and 5.3 µg/ml, respectively) and afatinib (IC = 5.4 and 11.4 µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC values at micromolar levels (IC range of 16.01-1.11 µM) compared with the reference drugs sorafenib (IC = 1.14 µM) and erlotinib (IC = 0.1 µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.

Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition

“…Antitumor evaluation using the MTT assay 4a,b,5a,b,6a,b,8,10,11,13, and 14 were screened for their in vitro antitumor activity by using the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against five human cancers: HePG2, HCT-116, MCF-7, PC3, and HeLa cell lines 39 . The antitumor activities of the synthesised compounds 3-14 and the reference drugs, celecoxib, afatinib, and doxorubicin, are shown in Table 1 25.6, 29.54, 31.28, 30.69, and 36.08 lM, respectively), afatinib (IC 50 values of 5.4, 11.4, 7.1, 7.7, and 6.2 lM, respectively), and doxorubicin (IC 50 values of 4.…”

“…Cancer, the uncontrolled growth of cells that invade adjacent healthy tissues, is the most fatal disease in the world 1 . Therefore, the design and synthesis of new molecules with promising and potential antitumor activity is of great importance [1][2][3][4][5][6][7][8][9][10] . The clinical use of drug combinations has led to various side effects, whereas the use of single molecules that target multiple molecular mechanisms is the currently preferred therapeutic strategy and is under investigation by medicinal chemists [11][12][13] .…”

“…Recently, curcumin was shown to have in vitro anti-angiogenic effects and in vivo anticancer activity through the inhibition of PDE isoenzymes 35 . Indeed, several compounds possessing heterocyclic core structures, such as quinazoline 2-4 , quinoline 9,10 , pyrimidine 36 , pyridine 9 , imidazole 6 , have potential antitumor activity.…”

Crystal structure of 6-iodo-3-phenyl-2-propylquinazolin-4(3H)-one, C17H15IN2O

“…In our laboratory, research efforts have concentrated on synthesizing quinazoline derivatives with substituted moieties having high lipophilic properties in the hope of developing effective and safe compounds [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Herein, we report the crystal structure of 6-iodo-3-phenyl-2-propylquinazolin-4(3H)-one as a methaqualone analogue.…”

Quinoline and ferrocene conjugates: Synthesis, computational study and biological evaluations

“…On the other hand, quinoline and quinolone scaffolds play an important role in anticancer drug development as their derivatives have shown activity through diverse mechanisms of action, such as growth inhibitors by cell cycle arrest, apoptosis, abrogation of cell migration, inhibition of angiogenesis and disregulation of nuclear receptor signaling . A series of quinoline derivatives containing additional aromatic rings have been reported to possess potent anticancer activities .…”