RESEARCH ARTICLE


The Synthesis of a Novel Anticancer Compound, N-(3,5 Dimethoxyphenyl) Acridin-9-Amine and Evaluation of Its Toxicity



Nur A. Ismail1, Abbas A. Salman1, Mohd S. M. Yusof2, Siti K. C. Soh3, Hapipah M. Ali1, Rozie Sarip1, *
1 Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia
2 School of Fundamental Sciences, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia
3 School of Marine and Environmental Sciences, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia


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© 2018 Ismail et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia; Tel: +603 7967 7022; E-mail: rozie@um.edu.my


Abstract

Introduction:

Acridine is a class of organic compounds which offers a wide range of biological and physical properties due to its unique chemical skeleton. A lot of researches have focused on the moulding of the substituents of the acridine ring system in an attempt to enhance its biological applications, especially in terms of anticancers, antioxidants, and antivirals.

Materials and Methods:

In this study, a new compound N-(3,5-dimethoxyphenyl)acridin-9-amine (G4) was synthesized through the Ullmann condensation of 2-chlorobenzoic acid and 3,5-dimethoxyaniline. In vitro cytotoxicity investigations of G4 on normal cell (WRL 68) and cancer cell lines (MCF-7, HT29 and HL60) were then conducted. In vivo evaluation or acute toxicology, was also carried out whereby male and female mice were administered G4 orally in single doses of 0 (control group), 500, and 1000 mg/kg.

Results:

As per the results, G4 exhibited in vitro antiproliferative activity on all the cancer cell lines tested. Also, no signs of toxicity were observed in the mice even after being administered the highest dose of G4. The structure of the compound was determined by single crystal X-ray diffraction analysis, CHN elemental analysis, Fourier Transformed Infrared (FTIR), 1H nuclear magnetic resonance (NMR), and 13C attached proton test (APT) NMR. G4 was found to be slightly planar and in discrete asymmetric units.

Conclusion:

The acridine was observed to be bound to 3,5-dimethoxyaniline (N1) as the confirmed G4 molecule. Also, the exocyclic carbon at position C13 was found to be monodentate and slightly planar. G4 exhibited profound antiproliferative activity towards HL60 cancer cell lines.

Keywords: Acridine, Heterocycle, N-(3,5- Dimethoxyphenyl)acridin-9-amine, Acute toxicity, Antiproliferative, Anticancers.