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dc.contributor.author
Emam, Aya M.
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Dahal, Achyut
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Singh, Sitanshu S.
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Tosso, Rodrigo David
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Ibrahim, Samy M.
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El Sadek, Mohamed
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Jois, Seetharama D.
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Enriz, Ricardo Daniel
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Kothayer, Hend
dc.date.available
2022-01-31T12:08:31Z
dc.date.issued
2021-09
dc.identifier.citation
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
dc.identifier.issn
0365-6233
dc.identifier.uri
http://hdl.handle.net/11336/150958
dc.description.abstract
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).
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley VCH Verlag
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
DOCKING
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DUAL ANTI-TB AND ANTICANCER
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EGFR INHIBITOR
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HYDRAZONE
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MOLECULAR DYNAMICS SIMULATIONS
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QUINAZOLINE
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Otras Ciencias Químicas
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Quinazoline-tethered hydrazone: A versatile scaffold toward dual anti-TB and EGFR inhibition activities in NSCLC
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-01-25T14:33:41Z
dc.journal.volume
354
dc.journal.number
12
dc.journal.pagination
1-16
dc.journal.pais
Alemania
dc.description.fil
Fil: Emam, Aya M.. Zagazig University; Egipto
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Fil: Dahal, Achyut. State University of Louisiana; Estados Unidos
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Fil: Singh, Sitanshu S.. State University of Louisiana; Estados Unidos
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Fil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
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Fil: Ibrahim, Samy M.. Zagazig University; Egipto
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Fil: El Sadek, Mohamed. Zagazig University; Egipto
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Fil: Jois, Seetharama D.. State University of Louisiana; Estados Unidos
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Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
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Fil: Kothayer, Hend. Zagazig University; Egipto
dc.journal.title
Archiv Der Pharmazie
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/ardp.202100281
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