Novel Imidazole Derivative: Inducing Apoptosis and Epigenetic Modulation in Human Lung Adenocarcinoma Cell Lines.

Posted: 11 Feb 2020

See all articles by Akshaya Rani A

Akshaya Rani A

Pondicherry University

Amrutha Arjunan

Independent

Arul Prakash Francis

Pondicherry university

Rukkumani Rajagopalan

Pondicherry University - Department of Biochemistry and Molecular Biology

Date Written: January 31, 2020

Abstract

Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazole derivatives are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel uracil derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. TBUEIB inhibited A549 cells at a dose of 106 ┬ÁM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound.

Keywords: anti-cancer, epigenetic, DNMT1, apoptosis, uracil derivatives

Suggested Citation

A, Akshaya Rani and Arjunan, Amrutha and Francis, Arul Prakash and Rajagopalan, Rukkumani, Novel Imidazole Derivative: Inducing Apoptosis and Epigenetic Modulation in Human Lung Adenocarcinoma Cell Lines. (January 31, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3533930

Akshaya Rani A (Contact Author)

Pondicherry University ( email )

India
605014 (Fax)

Amrutha Arjunan

Independent ( email )

Arul Prakash Francis

Pondicherry university ( email )

India

Rukkumani Rajagopalan

Pondicherry University - Department of Biochemistry and Molecular Biology ( email )

India

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