Synthesis and in vitro anticancer evaluation of some fused indazoles, quinazolines and quinolines as potential EGFR inhibitors.
Bioorg Chem
; 89: 102985, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-31121559
ABSTRACT
derivatives of benzo[g]indazole 5a, b, benzo[h]quinazoline 7, 12a-c, 13a-c and 15a-c and benzo[h]quinoline 17a-c and 19a-c were synthesized from 6-methoxy-3,4-dihydronaphthalen-1(2H)-one (1). Anticancer activity of all the synthesized compounds was evaluated against four cancerous cell lines; HepG2, MCF-7, HCT116 and Caco-2. MCF-7 cells emerged as the most sensitive cell line against the target compounds. All the examined compounds, except 5a and 5b, displayed potent to moderate anticancer activity against MCF-7 cells with an IC50 values ranging from 7.21 to 21.55⯵M. In particular, compounds 15c and 19b emerged as the most potent derivatives against EGFR-expressing MCF-7 cells with IC50 valuesâ¯=â¯7.70⯱â¯0.39 and 7.21⯱â¯0.43⯵M, respectively. Additionally, both compounds did not display any significant cytotoxicity towards normal BHK-21 fibroblast cells (IC50 valueâ¯>â¯200⯵M), thereby providing a good safety profile as anticancer agents. Furthermore, compounds 15c and 19b displayed potent inhibitory activity towards EGFR in the sub-micromolar range (IC50â¯=â¯0.13⯱â¯0.01 and 0.14⯱â¯0.01⯵M, respectively), compared to that of Erlotinib (IC50â¯=â¯0.11⯱â¯0.01⯵M). Docking studies for 15c and 19b into EGFR active site was carried out to explore their potential binding modes. Therefore, compounds 15c and 19b can be considered as interesting candidates for further development of more potent anticancer agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Quinazolinas
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Quinolinas
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Inhibidores de Proteínas Quinasas
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Receptores ErbB
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Indazoles
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2019
Tipo del documento:
Article