Evaluation of Synthetic 2,4-Disubstituted-benzo[g]quinoxaline Derivatives as Potential Anticancer Agents.

Islam Zaki,Ali H Abu Almaaty,Ahmed S Saad,Sara A Abu El-Ata,Ola A Abu Ali,Eman Fayad

doi:10.3390/ph14090853

Islam Zaki, Ali H Abu Almaaty + Show 4 more

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https://doi.org/10.3390/ph14090853

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Abstract

A new series of 2,4-disubstituted benzo[g]quinoxaline molecules have been synthesized, using naphthalene-2,3-diamine and 1,4-dibromonaphthalene-2,3-diamine as the key starting materials. The structures of the new compounds were confirmed by spectral data along with elemental microanalyses. The cytotoxic activity of all synthesized benzo[g]quinoxaline derivatives was assessed in vitro against the breast MCF-7 cancer cell line. The tested molecules revealed good cytotoxicity toward the breast MCF-7 cancer cell line, especially compound 3. The results of topoisomerase IIβ inhibition assay revealed that compound 3 exhibits potent inhibitory activity in submicromolar concentration. Additionally, compound 3 was found to cause pre-G1 apoptosis, and slightly increase the cell population at G1 and S phases of the cell cycle profile in MCF-7 cells. Finally, compound 3 induces apoptosis via Bax activation and downregulation of Bcl2, as revealed by ELISA assay.

Highlights

Cancer is one of the most challenging problems worldwide [1]
The results revealed that the tested benzo[g]quinoxaline revealed that the tested benzo[g]quinoxaline molecule 3 had a good inhibitory activity molecule 3 had a good inhibitory activity against topo IIβ at submicromolar level with against topo IIβ at submicromolar level with IC50 = 32.16 μM compared with value of
A series of 2,4-disubstituted benzo[g]quinoxaline molecules were synthesized, and their in vitro cytotoxic activity were evaluated against the breast MCF-7 cancer cell line using MTT colorimetric assay

Summary

Introduction

Cancer is one of the most challenging problems worldwide [1]. Breast cancer exceeds lung cancer in terms of mortality rate, with more than two million patients every year (more than 6.9% mortality rate) [2,3]. Targeted therapy has become an important type of cancer treatment, as it could reduce the activity of a specific target or prevent binding to a specific receptor [4,5]. A lot of efforts of pharmaceutical companies in the development of anticancer drugs have focused on targeted therapy for the treatment of different types of cancer [6,7]. Due to the rapid progress in understanding the molecular pathways involved in cell cycle regulation, there is a motivation to target different steps during cell cycle, in order to control cancer cell proliferation and to avoid drawbacks observed with traditional chemotherapeutic agents [8,9,10]. Apoptosis induction in cancer cells can be used as a new weapon against cancer cell proliferation [13,14]

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