The synthesis of trifluoromethylated N-nitroaryl-2-amino-1,3-dichloropropane derivatives and their evaluation as potential anti-cancer agents

Lucy Chappel; Lai Chun Wong; Chee-Onn Leong; Chun-Wai Mai; Ian T Meikle; Stephen P Stanforth; Thang V Truong

doi:10.1016/j.bmcl.2019.126910

The synthesis of trifluoromethylated N-nitroaryl-2-amino-1,3-dichloropropane derivatives and their evaluation as potential anti-cancer agents

Bioorg Med Chem Lett. 2020 Feb 15;30(4):126910. doi: 10.1016/j.bmcl.2019.126910. Epub 2019 Dec 19.

Authors

Lucy Chappel¹, Lai Chun Wong², Chee-Onn Leong³, Chun-Wai Mai⁴, Ian T Meikle¹, Stephen P Stanforth⁵, Thang V Truong¹

Affiliations

¹ Department of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
² Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University Malaysia, 57000 Kuala Lumpur, Malaysia.
³ Centre for Cancer and Stem Cells Research, Institute for Research, Development and Innovation, International Medical University Malaysia, 57000 Kuala Lumpur, Malaysia; Department of Life Sciences, School of Pharmacy, International Medical University Malaysia, 57000 Kuala Lumpur, Malaysia.
⁴ Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University Malaysia, 57000 Kuala Lumpur, Malaysia; Centre for Cancer and Stem Cells Research, Institute for Research, Development and Innovation, International Medical University Malaysia, 57000 Kuala Lumpur, Malaysia.
⁵ Department of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK. Electronic address: [email protected].

PMID: 31882300
DOI: 10.1016/j.bmcl.2019.126910

Abstract

Six N-nitroaryl-2-amino-1,3-dichloropropane derivatives have been prepared and evaluated against 18 cancer cell lines and two non-cancerous cell lines. Analysis of cell viability data and IC₅₀ values indicated that the presence of a trifluoromethyl group in the nitroaryl moiety is an important structural feature associated with the compounds' cytotoxicities.

Keywords: Anti-cancer agents; Nitroaromatic drugs; Nitrogen mustards; Trifluoromethylated drugs.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Line
Cell Survival / drug effects
Drug Screening Assays, Antitumor
Humans
Methylation
Prodrugs / chemical synthesis
Prodrugs / chemistry
Prodrugs / pharmacology
Propane / analogs & derivatives*
Propane / chemical synthesis
Propane / chemistry
Propane / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Prodrugs
1,3-dichloropropane
Propane