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 IC50 range of 7.7–14.2 µg/ml, in comparison with the reference drugs 5-fluorouracil (IC50 = 7.9 and 5.3 µg/ml, respectively) and afatinib (IC50 = 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 IC50 values at micromolar levels (IC50 range of 16.01–1.11 µM) compared with the reference drugs sorafenib (IC50 = 1.14 µM) and erlotinib (IC50 = 0.1 µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.
Highlights
IntroductionNeratinib and pelitinib (Figure 1), which are potent Epidermal growth factor receptors (EGFR) kinase inhibitors[31–38]
Development of a novel antitumour drug with potent activity remains critically important due to the majority of human deaths globally being attributable to cancer[1–13]
Epidermal growth factor receptors (EGFR) are an important class of kinase enzymes used in cancer treatment, which are overexpressed in several tumours, such as brain, liver, colon, prostate, breast, and non-small-cell lung cancers[14–18]
Summary
Neratinib and pelitinib (Figure 1), which are potent EGFR kinase inhibitors[31–38]. This bioisosteric replacement[39] did not require a water molecule to mediate the binding with the amino acid residue Thr766. 2-Styrylquinoline (SQ) derivatives have been reported as promising antitumour compounds against several tumour cell lines[40–43]. A series of 2-styryl-4-aminoquinoline (SQ-I, Figure 1) was developed which possessed potent in vitro antiproliferative activity against lung, colon, and liver cancer cell lines, comparable to gefitinib[44]. The antitumour activity of the target compounds was evaluated using two tumour cell lines, namely, human hepato-cellular carcinoma cell line (HepG2) and human colorectal carcinoma cell line (HCT116)[45–48]. Some compounds were evaluated for their inhibitory activity against the EGFR tyrosine kinase enzyme.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
