Affiliations 

  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014. Saudi Arabia
  • 2 Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014. Saudi Arabia
  • 3 School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang. Malaysia
  • 4 Department of Pharmacology, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014. Saudi Arabia
  • 5 College of Pharmacy, Northern Border University, Rafha. 0
  • 6 Department of Chemistry, University of Sargodha, Sargodha 40100. Pakistan
Med Chem, 2020 Sep 05.
PMID: 32888274 DOI: 10.2174/1573406416666200905125038

Abstract

BACKGROUND: Ligustrazine and chalcones have been reported previously for various biological activities including anticancer effects.

OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine based chalcones, in current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on growth of five different types of cancer cells.

METHODS: All compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.

RESULTS: Majority of compounds exhibited strong inhibition of cancer cells especially synthetic compounds 4a and 4b bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in main structural backbone were found most powerful inhibitors of cancer cell growth. Most active 9 compounds among whole series were selected for further studies related to different cancer targets including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.

CONCLUSION: Synthetic derivatives including 4a-b and 5a-b showed multitarget approach and showed strong inhibitory effects on EGFR, FAK and BRAF while three compounds including 3e bearing methoxy substitution, 4a and 4b with 1- pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.