Artículo
Quinazoline-tethered hydrazone: A versatile scaffold toward dual anti-TB and EGFR inhibition activities in NSCLC
Emam, Aya M.; Dahal, Achyut; Singh, Sitanshu S.; Tosso, Rodrigo David
; Ibrahim, Samy M.; El Sadek, Mohamed; Jois, Seetharama D.; Enriz, Ricardo Daniel
; Kothayer, Hend
Fecha de publicación:
09/2021
Editorial:
Wiley VCH Verlag
Revista:
Archiv Der Pharmazie
ISSN:
0365-6233
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Globally, lung cancer and tuberculosis are considered to be very serious and complex diseases. Evidence suggests that chronic infection with tuberculosis (TB) can often lead to lung tumors; therefore, developing drugs that target both diseases is of great clinical significance. In our study, we designed and synthesized a suite of 14 new quinazolinones (5a–n) and performed biological investigations of these compounds in Mycobacterium tuberculosis (MTB) and cancer cell lines. In addition, we conducted a molecular modeling study to determine the mechanism of action of these compounds at the molecular level. Compounds that showed anticancer activity in the preliminary screening were further evaluated in three cancer cell lines (A549, Calu-3, and BT-474 cells) and characterized in an epidermal growth factor receptor (EGFR) binding assay. Cytotoxicity in noncancerous lung fibroblast cells was also evaluated to obtain safety data. Our theoretical and experimental studies indicated that our compounds showed a mechanism of action similar to that of erlotinib by inhibiting the EGFR tyrosine kinase. In turn, the antituberculosis activity of these compounds would be produced by the inhibition of enoyl-ACP-reductase. From our findings, we were able to identify two potential lead compounds (5i and 5l) with dual activity and elevated safety toward noncancerous lung fibroblast cells. In addition, our data identified three compounds with excellent anti-TB activities (compounds 5i, 5l, and 5n).
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Articulos(CCT - SAN LUIS)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SAN LUIS
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SAN LUIS
Articulos(IMIBIO-SL)
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Citación
Emam, Aya M.; Dahal, Achyut; Singh, Sitanshu S.; Tosso, Rodrigo David; Ibrahim, Samy M.; et al.; Quinazoline-tethered hydrazone: A versatile scaffold toward dual anti-TB and EGFR inhibition activities in NSCLC; Wiley VCH Verlag; Archiv Der Pharmazie; 354; 12; 9-2021; 1-16
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