Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors.
Bioorg Chem
; 69: 7-19, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27656775
ABSTRACT
A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10µM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.01, 0.1, 1, 10 and 100µM) to obtain GI50 values ranging from 1.30 to 5.64µM. Flow cytometric analysis revealed that compound 8q arrests the A549 cells in sub G1 phase followed by induction of apoptosis which was further confirmed by Annexin-V-FITC, Hoechst nuclear staining, caspase 3 activation, measurement of mitochondrial membrane potential and ROS generation. Topo II mediated DNA relaxation assay results showed that conjugate 8q could significantly inhibit the activity of topo II. Moreover, molecular docking studies also indicated binding to the topoisomerase enzyme (PDBID 1ZXN).
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxidiazóis
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Piridinas
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Apoptose
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Proteínas de Ligação a DNA
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Inibidores da Topoisomerase II
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article