Format

Send to

Choose Destination
Anticancer Agents Med Chem. 2019 Sep 6. doi: 10.2174/1871520619666190906162537. [Epub ahead of print]

Synthesis of Substituted Cinnamido Linked Quinazolinone Congeners as Potential Anticancer Agents via Mitochondrial Dependent Intrinsic Apoptotic Pathway.

Author information

1
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad-500037. India.
2
Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad-500037. India.
3
Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007. India.

Abstract

BACKGROUND:

The synthesis of novel heterocyclic scaffolds with amide functionality is a key research area due to their plethora of medicinal applications. Present study aims to explore the synthesis of new cinnamido linked quinazolinone congeners and their potential as anticancer agents.

METHODS:

Cytotoxicity evaluation, Cell cycle analysis, JC-1 staining, ROS, Annexin V assays, AO/EB, DAPI nuclear staining, Colony forming assay and Western blot analysis.

RESULTS:

Among the synthesized compounds 5eb and 5fc have shown promising cytotoxic activity with an IC50 value of 3.89±1.01µM and 4.05±0.62µM against HeLa cell lines. Flow-cytometry analysis demonstrated that the compound 5eb arrest the sub-G1 phase of cell cycle and induce apoptosis. Furthermore the compound 5eb trigger the collapse of mitochondrial membrane potential (ΔѰm), which was assessed by JC-1 staining and also induce the generation of Reactive Oxygen Species. Increase in the expression of pro-apoptotic proteins such as Bax, p53, cleaved PARP and cleaved caspase-3 by 5eb confirms the activation of mitochondrial dependent intrinsic apoptosis pathway.

CONCLUSION:

Our results suggest that compound 5eb and 5fc of cinnamido linked quinazolinone derivatives could serve as potential leads in the development of novel chemotherapeutic agents.

KEYWORDS:

Quinazolinones; apoptosis mechanism; cinnamic acids; cinnamides; cytotoxicity

Supplemental Content

Loading ...
Support Center