Synthesis and evaluation of novel α-substituted chalcones with potent anti-cancer activities and ability to overcome multidrug resistance

Sharon Riaz; Maheen Iqbal; Rahim Ullah; Rida Zahra; Ghayoor Abbas Chotana; Amir Faisal; Rahman Shah Zaib Saleem

doi:10.1016/j.bioorg.2019.03.014

Synthesis and evaluation of novel α-substituted chalcones with potent anti-cancer activities and ability to overcome multidrug resistance

Bioorg Chem. 2019 Jun:87:123-135. doi: 10.1016/j.bioorg.2019.03.014. Epub 2019 Mar 7.

Authors

Sharon Riaz¹, Maheen Iqbal², Rahim Ullah², Rida Zahra², Ghayoor Abbas Chotana¹, Amir Faisal³, Rahman Shah Zaib Saleem⁴

Affiliations

¹ Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.
² Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.
³ Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan. Electronic address: [email protected].
⁴ Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan. Electronic address: [email protected].

PMID: 30884306
DOI: 10.1016/j.bioorg.2019.03.014

Abstract

A series of forty α-substituted chalcones were synthesized and screened for their antiproliferative activities against HCT116 (colorectal) and HCC1954 (breast) cancer cell lines. Compounds 5a and 5e were found to be the most potent compounds with GI₅₀ values of 0.63 µM and 0.725 µM in HCC1954 cell line and 0.69 µM and 1.59 µM in HCT116 cell line, respectively. Both compounds induced a G2/M cell cycle arrest and caused apoptotic cell death in HCT116 cells as shown by the induction of PARP cleavage. The compounds also stabilized p53 in a dose-dependent manner in HCT116 cells following 24-hour treatment. Furthermore, both 5a and 5e were able to overcome multidrug resistance in two MDR-1 overexpressing multidrug resistant cell lines.

Keywords: Antiproliferative activity; Apoptotic activity; Cell cycle arrest; Multidrug resistance; α-substituted chalcones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Cycle / drug effects
Cell Proliferation / drug effects
Chalcones / chemical synthesis
Chalcones / chemistry
Chalcones / pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Multiple / drug effects*
Drug Resistance, Neoplasm / drug effects*
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Molecular Structure
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Chalcones