Design and Synthesis of Some New Quinoxaline-1,2,4-Oxadiazole-Amide Conjugates as EGFR Targeting Agents and ADMET Studies

The synthesis of some new quinoxaline-1,2,4-oxadiazole-amide conjugates (6a-n) was described, and their structures were determined using 1 HNMR, 13 CNMR, and mass spectral analysis. The in vitro anti-cancer activity of the compounds (6a-n) against three human cancer cell lines such as MCF-7 (breast)...

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Bibliographic Details
Published in:Polycyclic aromatic compounds 2024-09, Vol.44 (8), p.5504-5517
Main Authors: Kurma, Srimathi, Nukala, Satheesh Kumar, Thirukovela, Narasimha Swamy, Badithapuram, Vinitha, Dasari, Gouthami, Bandari, Srinivas
Format: Article
Language:English
Subjects:
ADMET studies
Antitumor activity
Cancer
Conjugates
Epidermal growth factor receptors
Etoposide
in vitro anti-cancer activity
Kinases
Molecular docking
Oxadiazoles
Pharmacokinetics
Quinoxaline
quinoxaline-1,2,4-oxadiazole-amide conjugates
Quinoxalines
SARs
Spectral analysis
Spectrum analysis
Synthesis
Tumor cell lines
Tyrosine
tyrosine kinase EGFR inhibitory activity
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Summary:The synthesis of some new quinoxaline-1,2,4-oxadiazole-amide conjugates (6a-n) was described, and their structures were determined using 1 HNMR, 13 CNMR, and mass spectral analysis. The in vitro anti-cancer activity of the compounds (6a-n) against three human cancer cell lines such as MCF-7 (breast), HepG2 (lung), and DU-145 (prostate) revealed that the compounds 6d, 6e, and 6f exhibited promising activity against three cancer cell lines. Predominantly, compound 6f demonstrated greater activity than the standard drug Etoposide on MCF-7, HepG2, and DU-145 with IC 50 values of 0.82 ± 0.01, 1.30 ± 0.02, and 2.12 ± 0.04 µM, respectively. Furthermore, the compounds 6e and 6f displayed promising inhibitory activity over the tyrosine kinase EGFR when compared with the standard Erlotinib. Molecular docking studies carried out on three potent compounds (6d, 6e, and 6f) on the EGFR receptor recommended that the compound 6f strongly binds to protein EGFR (pdbid: 4HJO). In addition, the in silico pharmacokinetic profile was also achieved for the three potent compounds 6d, 6e, and 6f using SWISS/ADME and pk CSM. Results showed that the compounds 6d, 6e, and 6f followed the Lipinski rule, Veber rule, Egan rule, Ghose rule, and Muegge rule without any deviation.
ISSN:1040-6638
1563-5333
DOI:10.1080/10406638.2023.2265027