ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

O-Allyloxy chalcone derivatives: design, synthesis, anticancer activity, network pharmacology and molecular docking

Shweta Umar, Sudhir Katariya, Rina Soni, Shubhangi S. Soman, and B. Suresh

Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India

E-mail: src_rina@outlook.com

Received: 29 January 2024  Accepted: 1 October 2024

Abstract:

A series of (2E)-3-[2,4-bis(2-propen-1-yloxy)phenyl]-1-phenyl]-2-propen-1-ones—chalcone derivatives with O-allyloxy groups—were synthesized in good yields and characterized by different analytical techniques. Their anticancer activity was evaluated against the A549 (lung cancer) cell line. The most active compounds of this series were the 1-(4-fluorophenyl derivative 9c (IC₅₀ = 0.48 ± 0.07 µM) and the 1-(4-octyloxy)phenyl derivative 9f (IC₅₀ = 0.04 ± 0.01 µM). Network pharmacology analysis using the SwissTarget and DisGeNet databases identified potential targets for 9c in the Non-Small Cell Lung Carcinoma (NSCLC) cell line. Protein–Protein Interaction (PPI) network analysis revealed seven hub genes: MAPK14, PTGS2, HSP90AA1, MAPK8, NOS2, SYK, and NR3C1. Gene ontology analysis highlighted diverse biological functions. KEGG pathway analysis implicated pathways in cancer and immunoregulation. Molecular docking analysis suggested a strong interaction between 9c with MAPK14 (calculated docking score of  –8.4 kcal mol^–1). Compound 9c's potent activity warrants further preclinical and clinical evaluation as a potential NSCLC therapy Based on this results, study of heterocyclic compounds with O-allyloxy groups will help to explore their impact on anticancer activity and mechanistic pathway.

Keywords: O-allyloxy chalcone; Chalcone; Anticancer; Molecular docking; Lung cancer

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03723-9

Chemical Papers 78 (16) 8903–8917 (2024)