Design, synthesis and biological evaluation of novel imidazole-chalcone derivatives as potential anticancer agents and tubulin polymerization inhibitors
- PMID: 33933802
- DOI: 10.1016/j.bioorg.2021.104904
Design, synthesis and biological evaluation of novel imidazole-chalcone derivatives as potential anticancer agents and tubulin polymerization inhibitors
Abstract
Novel imidazole-chalcone derivatives were designed and synthesized as tubulin polymerization inhibitors and anticancer agents. The antiproliferative activity of the imidazole-chalcone was assessed on some human cancer cell lines including A549 (adenocarcinoma human alveolar basal epithelial cells), MCF-7 (human breast cancer cells), MCF-7/MX (mitoxantrone resistant human breast cancer cells), and HEPG2 (human hepatocellular carcinoma cells). Generally, the imidazole-chalcone derivatives exhibited more cytotoxicity on A549 cancer cells in comparison to the other three cell lines, among them compounds 9j' and 9g showed significant cytotoxicity with IC50 values ranging from 7.05 to 63.43 μM against all the four human cancer cells. The flow cytometry analysis of A549 cancer cells treated with 9g and 9j' displayed that these compounds induced cell cycle arrest at the G2/M phase at low concentrations and increased the number of apoptotic cells (cells in subG1 phase) at higher concentrations. They have also inhibited tubulin polymerization similar to combretastatin A-4 (CA-4). Annexin V binding staining assay in A549 cancer cells revealed that compound 9j' induced apoptosis (early and late). Finally, molecular docking studies of 9j' into the colchicine-binding site of tubulin presented the probable interactions of these compounds with tubulin.
Keywords: Anticancer activity; Apoptosis; Chalcone; Imidazole; Molecular docking; Tubulin inhibitors.
Copyright © 2021 Elsevier Inc. All rights reserved.
Similar articles
-
Design and synthesis of novel imidazole-chalcone derivatives as microtubule protein polymerization inhibitors to treat cervical cancer and reverse cisplatin resistance.Bioorg Chem. 2024 Jun;147:107310. doi: 10.1016/j.bioorg.2024.107310. Epub 2024 Apr 4. Bioorg Chem. 2024. PMID: 38583249
-
Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents.Bioorg Med Chem. 2014 Apr 1;22(7):2060-79. doi: 10.1016/j.bmc.2014.02.028. Epub 2014 Mar 1. Bioorg Med Chem. 2014. PMID: 24629450
-
Novel HDAC/Tubulin Dual Inhibitor: Design, Synthesis and Docking Studies of α-Phthalimido-Chalcone Hybrids as Potential Anticancer Agents with Apoptosis-Inducing Activity.Drug Des Devel Ther. 2020 Aug 3;14:3111-3130. doi: 10.2147/DDDT.S256756. eCollection 2020. Drug Des Devel Ther. 2020. PMID: 32848361 Free PMC article.
-
Two Important Anticancer Mechanisms of Natural and Synthetic Chalcones.Int J Mol Sci. 2022 Sep 30;23(19):11595. doi: 10.3390/ijms231911595. Int J Mol Sci. 2022. PMID: 36232899 Free PMC article. Review.
-
A review on Millepachine and its derivatives as potential multitarget anticancer agents.Biochem Biophys Res Commun. 2023 Nov 12;681:249-270. doi: 10.1016/j.bbrc.2023.09.044. Epub 2023 Sep 19. Biochem Biophys Res Commun. 2023. PMID: 37793311 Review.
Cited by
-
Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective.Pharmaceuticals (Basel). 2023 Feb 14;16(2):299. doi: 10.3390/ph16020299. Pharmaceuticals (Basel). 2023. PMID: 37259442 Free PMC article. Review.
-
Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents.Molecules. 2022 Jul 20;27(14):4621. doi: 10.3390/molecules27144621. Molecules. 2022. PMID: 35889493 Free PMC article.
-
Design and Synthesis of Novel α-Methylchalcone Derivatives, Anti-Cervical Cancer Activity, and Reversal of Drug Resistance in HeLa/DDP Cells.Molecules. 2023 Nov 21;28(23):7697. doi: 10.3390/molecules28237697. Molecules. 2023. PMID: 38067428 Free PMC article.
-
Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry.Pharmaceuticals (Basel). 2022 Oct 11;15(10):1250. doi: 10.3390/ph15101250. Pharmaceuticals (Basel). 2022. PMID: 36297362 Free PMC article. Review.
-
Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy.Biomolecules. 2022 Dec 10;12(12):1843. doi: 10.3390/biom12121843. Biomolecules. 2022. PMID: 36551271 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
