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Design, Synthesis, Molecular Docking, Antiapoptotic and Caspase-3 Inhibition of New 1,2,3-Triazole/Bis-2(1H)-Quinolinone Hybrids

El-Sheref, E. M.; Aly, A. A.; Alshammari, M. B.; Brown, A. B.; Abdel-Hafez, S. M. N.; Abdelzaher, W. Y.; Bräse, S.; Abdelhafez, E. M. N.

Abstract:
A series of novel 1,2,3-triazoles hybridized with two quinolin-2-ones, was designed and synthesized through click reactions. The structures of the synthesized compounds were elucidated by NMR, IR, and mass spectra in addition to elemental analysis. The synthesized compounds were assessed for their antiapoptotic activity in testis, as testicular torsion is the main cause of male infertility. This effect was studied in light of decreasing tissue damage induced by I/R in the testis of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Compounds 6a–c were the most active antiapoptotic hybrids with significant measurements for malondialdehyde (MDA) and total antioxidant capacity (TAC) and the apoptotic biomarkers (testicular testosterone, TNFα, and caspase-3) in comparison to the reference. A preliminary mechanistic study was performed to improve the antiapoptotic activity through caspase-3 inhibition. A compound assigned as 6-methoxy-4-(4-(((2-oxo-1,2-dihydroquinolin-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one (6c) was selected as a representative of the most active hybrids in comparison to NAC. Assay of cytochrome C for 6c revealed an attenuation of cytochrome C level about 3.54 fold, comparable to NAC (4.13 fold). ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000126500
Veröffentlicht am 20.11.2020
Originalveröffentlichung
DOI: 10.3390/molecules25215057
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 30.10.2020
Sprache Englisch
Identifikator ISSN: 1420-3049
KITopen-ID: 1000126500
Erschienen in Molecules
Band 25
Heft 21
Seiten Art. Nr.: 5057
Schlagwörter caspase-3, 1,2,3-triazole-biquinolin-2-one, antiapoptotic; NAC, histopathology, antioxidant, testis, docking
Nachgewiesen in Scopus
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