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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

The Identification of a Novel Unsymmetrical Azine as an Apoptosis Inducer in Colorectal Cancer

Author(s): Fahad M. Almutairi , Ayat G. Ali , Abdou O. Abdelhamid, Adel I. Alalawy, Mai K. Bishr and Mervat S. Mohamed*

Volume 21 , Issue 3 , 2021

Published on: 24 August, 2020

Page: [406 - 413] Pages: 8

DOI: 10.2174/1871520620666200824095314

Price: $65

Abstract

Background: Defects in the physiological mechanisms of apoptosis are one of the pivotal factors implicated in carcinogenesis. Thus, the development of novel compounds that target various apoptotic pathways has provided promising anticancer therapeutic opportunities.

Objective: This study explores the cytotoxic effects of a novel unsymmetrical azine against specific cancer cell lines and investigates the mechanism of cytotoxicity.

Methods: Molecular modeling was used to test the binding affinity of four new unsymmetrical azines to a model of an apoptosis inhibitor protein (XIAP). The compound with the highest binding affinity, C4, was further tested on different cell lines. Real-time Polymerase Chain Reaction (PCR) and Transmission Electron Microscope (TEM) were used to study apoptosis induction biochemically and morphologically.

Results: In comparison to cisplatin as a control, the compound C4 exhibited notable cytotoxicity against all tested cancer cell lines, especially the human colorectal carcinoma cell line (HCT-116). Furthermore, C4-treated cells demonstrated marked overexpression of the pro-apoptotic proteins Bax and caspase-3 as well as the tumor suppressor p53. On the other hand, the expression of the anti-apoptotic protein Bcl-2 was inhibited. On TEM examination, C4-treated HCT-116 cells showed classical structural signs of apoptosis.

Conclusion: This study identifies a novel azine (C4), which induces remarkable cytotoxicity against the colorectal carcinoma cell line, mediated through apoptosis induction. These novel insights suggest C4 as a promising therapeutic agent in colorectal cancer.

Keywords: Unsymmetrical azines, molecular modeling, cytotoxicity, apoptosis, morphological changes, XIAP, colorectal cancer.

Graphical Abstract
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