Abstract

The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis was assessed to evaluate the possible pathways induced by compound A and B. MTT assay results using A and B showed significant inhibition of MCF-7 cell viability, with IC50 values of 3. 27 ± 0.171 and 4.36 ± 0.219 μg/mL, respectively, after a 72 hour treatment period. Compound A and B did not demonstrate significant cytotoxic effects towards MDA-MB-231, WRL-68 and MCF-10A cells. Acute toxicity tests also revealed an absence of toxic effects on mice. Fluorescent microscopic studies confirmed distinct morphological changes (membrane blebbing and chromosome condensation) corresponding to typical apoptotic features in treated MCF-7 cells. Using Cellomics High Content Screening (HCS), we found that compound A and B could trigger the release of cytochrome c from mitochondria to the cytosol. The release of cytochrome c activated the expression of caspases-9 and then stimulated downstream executioner caspase-3/7. In addition, caspase-8 showed remarkable activity, followed by inhibition of NF-κB activation in A-and B-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways.

Highlights

  • The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells

  • Both of the absorption bands for the NH quinazoline ring and azomethine group are evident for the formation of both synthesized compounds

  • There are a wide variety of signals and stimuli that can trigger apoptosis, chemotherapy still offers the most effective approach to treat cancer by inducing apoptosis in cells with fewer side effects and higher efficiency

Read more

Summary

Introduction

The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The intrinsic signaling pathways stimulate apoptosis via the generation of intracellular signals that act directly on targets within the cell through mitochondrial initiated events when cytochrome c is released into the cytoplasm[5,6]. The final pathway of apoptosis, whether extrinsic or intrinsic, is the activation of the execution effector caspases, including caspase-3/6/712,13 These caspases activate cytoplasmic endonucleases, which degrade nuclear material, as well as proteases that lead to degradation of the nuclear and cytoskeletal proteins[14]. The quinazoline nucleus and its derivatives are a class of heterocyclic compounds that are considered to be the basic framework of biologically active compounds that exist in a number of drug molecules and biologically active compounds. As a continuation of previous efforts, researchers aim to synthesize and develop new active quinazolines by different synthetic routes to obtain a wide range of biological activities

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call