1,3,4-oxadiazole/chalcone hybrids: Design, synthesis, and inhibition of leukemia cell growth and EGFR, Src, IL-6 and STAT3 activities.

Abstract

A new series of 1,3,4-oxadiazole/chalcone hybrids was designed, synthesized, identified with different spectroscopic techniques and biologically evaluated as inhibitors of EGFR, Src, and IL-6. The synthesized compounds showed promising anticancer activity, particularly against leukemia, with 8v being the most potent. The synthesized compounds exhibited strong to moderate cytotoxic activities against K-562, KG-1a, and Jurkat leukemia cell lines in MTT assays. Compound 8v showed the strongest cytotoxic activity with IC50 of 1.95 µM, 2.36 µM and 3.45 µM against K-562, Jurkat and KG-1a leukemia cell lines, respectively. Moreover; the synthesized compounds inhibited EGFR, Src, and IL-6. Compound 8v was most effective at inhibiting EGFR (IC50 = 0.24 μM), Src (IC50 = 0.96 μM), and IL-6 (% of control = 20%). Additionally, most of the compounds decreased STAT3 activation.

• Authors: Marwa Ali A Fathi, Amer Ali Abd El-Hafeez, Dalia Abdelhamid, Samar H Abbas, Monica M Montano, Mohamed Abdel-Aziz
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 84 Pg. 150-163 (03 2019) ISSN: 1090-2120 [Electronic] United States
• PMID: 30502626 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Interleukin-6
• Oxadiazoles
• Protein Kinase Inhibitors
• STAT3 Transcription Factor
• STAT3 protein, human
• 1,3,4-oxadiazole
• Chalcone
• EGFR protein, human
• ErbB Receptors

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chalcone (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Design
• Drug Screening Assays, Antitumor
• ErbB Receptors (antagonists & inhibitors, metabolism)
• Humans
• Interleukin-6 (antagonists & inhibitors, metabolism)
• Molecular Structure
• Oxadiazoles (chemistry, pharmacology)
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Structure-Activity Relationship