Synthesis and in vitro exploration of the 8-carbo substituted 5-methoxyflavones as anti-breast and anti-lung cancer agents targeting protein kinases (VEGFR-2 & EGFR).

Autor: Nkoana JK; Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa., More GK; College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa., Mphahlele MJ; Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa. Electronic address: mphahmj@unisa.ac.za., Elhenawy AA; Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, 11884 Cairo, Egypt; Chemistry Department, Faculty of Science, Al-Baha University, Al-Baha 1988, Saudi Arabia.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107875. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.bioorg.2024.107875
Abstrakt: The 8-aryl-, 8-styryl- and 8-arylethynyl substituted 5-methoxyflavones were synthesized and characterized using a combination of spectroscopic techniques. Single crystal X-ray diffraction (XRD) study on a representative compound 3h shows an inverted dimer linked by fused ten and six-membered ring motifs involving intermolecular CO⋯HC and CH⋯OC hydrogen bonds. Compounds 3b, 3c, 3d, 4a and 4b exhibited strong activity against the human breast (MCF-7) cancer cell line (IC 50  = 13.68 ± 0.72, 16.91 ± 0.40, 13.63 ± 0.36, 14.66 ± 0.47 and 12.26 ± 0.45 μM, respectively) and lung (A549) cancer cell line (IC 50  = 15.38 ± 0.33, 10.00 ± 0.28, 12.38 ± 0.30, 12.84 ± 0.33 and 8.47 ± 0.30 μM, respectively) compared to quercetin (IC 50  = 40.61 ± 1.07 and 58.17 ± 0.50 μM, respectively). Compounds 3b, 3c and 4b exhibited dual inhibitory effect against the vascular endothelial growth factor receptor-2 (VEGFR-2) and the epidermal growth factor receptor (EGFR) tyrosine kinase phosphorylation. Molecular docking revealed that strong alignment with the enzyme backbone is achieved mostly by hydrophobic (π-π, and π-H) contacts and by hydrogen bonding interaction with the residues in the active sites of VEGFR-2 and EGFR. The test compounds possess favorable drug-likeness properties, supporting their potential as promising therapeutic candidates.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Malose Jack Mphahlele reports financial support and equipment, drugs, or supplies were provided by National Research Foundation (ZA). Malose J Mphahlele reports a relationship with National Research Foundation (SA) that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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