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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
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Effects of Alkoxy Chain Length and 1-Hydroxy Group on Anticolorectal Cancer Activity of 2-Bromoalkoxyanthraquinones

Nurhaliza Wati Mekzali1, Cheok Wui Chee2, Iskandar Abdullah1,3

  • 1Department of Chemistry, Drug Design and Development Research Group (DDDRG), Faculty of Science, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.

Medicinal Chemistry (Shariqah (United Arab Emirates))
|April 12, 2023
PubMed
Abstract

Insights

New 2-bromoalkoxyanthraquinones show promise for colorectal cancer treatment. A 1-hydroxy group and short alkoxy chain enhance anticancer activity, with compound 6b demonstrating significant antiproliferation and selectivity.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Drug Discovery

Background:

  • Colorectal cancer frequently involves KRAS and p53 genetic mutations.
  • Targeting these mutations offers a potential therapeutic strategy for colorectal cancer.

Purpose of the Study:

  • Investigate the impact of alkoxy chain length and a 1-hydroxy group on the anticolorectal cancer activity of 2-bromoalkoxyanthraquinones.
  • Corroborate in vitro findings with in silico analyses.

Main Methods:

  • Evaluated in vitro anticancer activity of 2-bromoalkoxyanthraquinones against HCT116, HT29, and CCD841 CoN cell lines.
  • Performed molecular docking to assess interactions with p53 and KRAS targets (7B4N and 6P0Z).

Main Results:

  • Compounds with a 1-hydroxy group exhibited enhanced anticancer activity compared to their counterparts.
  • Compound 6b (C3 alkoxy chain) showed potent antiproliferation against HCT116 cells (IC50 = 3.83 μM) with high selectivity (SI = 45.47).
  • Molecular docking indicated additional hydrogen bonds involving the 1-hydroxy group of compound 6b; it possesses favorable lipophilicity and ligand efficiency metrics.

Conclusions:

  • The 1-hydroxy group and short alkoxy chain are crucial for the anticolorectal cancer activity of 2-bromoalkoxyanthraquinones.
  • Compound 6b warrants further optimization as a potential therapeutic agent for colorectal cancer.
Keywords:
2-hydroxyanthraquinoneAlizarinalkylationantiproliferationcolorectal cancerin silicoside chain

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